Shoukat Dedhar, PhD
Distinguished Scientist - Genetics Unit, Integrative Oncology
firstname.lastname@example.org Rm 3-110 ▪ 675 West 10th Avenue, Vancouver, B.C., V5Z 1L3, Canada
Distinguished Scientist - Genetics Unit, Integrative Oncology, BC Cancer Research Centre
Professor Biochemistry and Molecular Biology, University of British Columbia
Robert L. Noble Prize (2013): Canadian Cancer Society Award of Research Excellence for Outstanding Achievement in Cancer Research Canadian Cancer Society
Major Research areas:
1. Cell-Extracellular Matrix interactions
2. Coordination of Integrin and Growth factor Signal Transduction
3. Physiological and Pathological roles of Integrin-Linked Kinase (ILK)
4. Mitotic Spindle Organization and Centrosome Clustering
5. Epithelial to Mesenchymal Transition (EMT) and Wnt Signaling
6. Models of Metastasis
7. Genes Regulating Metastatic Potential
8. Hypoxia and Carbonic Anhydrases IX and XII as Therapeutic Targets
9. Cancer cell Metabolism and Tumor Microenvironment
Key discoveries have been the identification of Integrin-mediated signaling pathways leading to regulation of cell proliferation, survival and migration. The discovery of Integrin-Linked Kinase (ILK) in 1996 in the Dedhar laboratory has demonstrated how integrin receptors on different types of cells coordinate signals to regulate cellular homeostasis. ILK is required for embryonic development, for the formation of blood vessels and for cardiac function. It is also essential for the regulation of the proper development of neurons as well as the function of other cell types such as chondrocytes, smooth muscle cells, skin cells and hair follicle cells.
ILK was found to induce oncogenic transformation of epithelial cells and subsequently has been shown to be expressed at abnormally high levels in many types of human cancers. In many cases the amount of ILK protein in cells predicts for long term patient survival, i.e. the higher the amount, the worse the prognosis, suggesting that ILK contributes to the disease process and to therapeutic resistance.
ILK activation promotes the survival and growth of tumor cells and also promotes the HIF-1 and VEGF mediated angiogenesis
Recent work using sophisticated Proteomics technology has revealed that ILK localizes to the centrosome, in addition of focal adhesions where integrins are present. In the centrosome ILK controls the assembly of the mitotic spindle during cell division. It also regulates the clustering of supernumerary centrosomes that exist in many cancer cells. The clustering of centrosomes in cancer cells allows them to survive and divide normally. Blocking the function of ILK in centrosomes in such cancer cells results in centrosome “declustering” and cell death. Therefore blocking ILK can induce the death of cancer cells but not of normal cells which o not require centrosome clustering.
ILK is a Cancer Therapeutic Target.
Inhibition of ILK activity suppresses tumor growth and progression to metastasis, and compounds that inhibit ILK activity are under development. Inhibitors developed so far appear to selectively kill tumor cells relative to “normal” counterparts. Collaborative research has shown that ILK inhibitors could be used therapeutically for breast cancer, prostate cancer, pancreatic cancer, colon cancer, non small cell lung cancer, malignant melanoma, glioblastoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML)
Models of Cancer Metastasis, Hypoxia and Carbonic Anhydrases IX and XII
Patient mortality results from the formation of metastases in distant (vital) organs. The metastatic potential of primary tumors is variable and likely depends of the biology of the tumor. We have established mouse models to study metastasis. Our initial work with breast cancer models of metastasis has identified a gene signature that is unique to metastatic tumors. Many of the genes are induced by “hypoxia” and function to protect the cells and promote survival in a hypoxic environment. Two of the genes CAIX and CAXII regulate the pH of the cells in hypoxia, and we have discovered that blocking the function of CAIX results in the death of the metastatic cells in a hypoxic environment, and in tumor regression as well as formation of metastasis.
Examination of the expression of CAIX in about 4000 breast cancer samples demonstrated that CAIX expression predicts for poor patient prognosis as well as for the formation of distant metastasis. Current work is focused on determining how CAIX controls the survival of hypoxic tumor cells and why it is needed for the formation of metastases. We are also developing compounds that could be used therapeutically to block CAIX function and also to image CAIX and identify hypoxic and potentially metastatic tumors.
An excellent summary of work on this topic by the Dedhar lab can be found here (links to PDF).
Shawn Chafe; Post Doc (CBCF Postdoctoral Fellowship award recipient 2013-2015)
Jordan Gillespie; Research Tech
Eva-Maria Hedlund; visiting Post Doc
Eiko Kawamura; Post doc
Yuanmei Lou; Research Scientist
Paul McDonald; Research Scientist
Edward Morris; Post doc
Mridula Swayampakula; Post doc
Marylou Vallejo Espi (Maria de Lourdes); Grad Student
Andrew Fielding, PhD: Post-Doctoral Fellow
Frances Lock, PhD: Post-Doctoral Fellow
Isabella Serano, PhD: Post-Doctoral Fellow
Mikola Maydan, PhD: Post-Doctoral Fellow
Jamie Lim, BSc: Graduate Student
Daiana Becker dos Santos, BSc: Graduate Student
Timothy McPhee, BSc: PhD student
Maria Lourdes, BSc: PhD student
Manuel Diego Puyol, PhD: Visiting Professor, Professor of Medicine, University of Alcala, Spain
Arusha Oloumi, PhD: Post-Doctoral Fellow
Iveta Dobreva, PhD: Post-Doctoral Fellow
Virginia Gray, MSc: Research Technician
Recent Research Funding:
Canadian Institute For Health Research (CIHR) Foundation Scheme, The Role of Tumor Microenvironment in Cancer Progression: Identification and Therapeutic Intervention of Novel Targets. 2015-2022; $4,164,493
Canadian Cancer Society Research Institute (CCSRI), New therapeautic strategy targeting tumour hypoxia and carbonic anhydrase IX for the treatment of pancreatic cancer. 2015-2020; $1,248,667
Canadian Institute For Health Research (CIHR), Development of therapeutic antibodies targeting Carbonic Anhydrase IX: 2014-2018; $609,976
Canadian Cancer Society Research Institute (CCSRI), Identification and development of novel anti-cancer agents targeting centrosome clustering in cancer cell: 2014-2016; $186,224
Pancreas Centre BC/BC Cancer Foundation/VGH Foundation, Evaluation of tumor hypoxia and therapeutic targeting of Carbonic Anhydrase IX and Integrin-linked kinase (ILK) in pancreatic cancer: 2013-2015; $94,620
BC Cancer Foundation, Evaluation of tumor hypoxia and therepeutic targeting of Carbonic Anhydrase IX/XII in pancreatic cancer: 2013-2014; $20,000
Canadian Cancer Society Research Institute (CCSRI), Cell-Extracellular Matrix Interactions in Differentiation and Oncogenesis: 2008-2013; $682,500
Canadian cancer Society Research Institute (CCSRI), Targeting stem cells to improve treatment of chronic myeloid leukemia: 2010-2013; $414,000. Co-Applicant. PI Dr Xiaoyan Jiang
Canadian Institutes for Health Research (CIHR), Regulation of Wnt signaling and Epithelial-Mesenchymal Transition by Integrin-Linked Kinase: 2007-2012; $645,000
Canadian Institutes for Health research (CIHR), Role of Integrin Linked Kinase in Mitotic spindle assembly and centrosome clustering in cancer cells. 2009-2014; $675,000
Canadian Institutes for Health research (CIHR), Targgeting carbonic anhydrase IX for the diagnosis and treatment of aggressive breast cancer; 2010-2015; $926,275
Terry Fox Foundation Program Project, Role of Integrin Linked Kinase in Prostate cancer progression; 2006-2011; $770,000
Canadian Breast Cancer Research Alliance (CBCRA), Models for the identification of novel molecular targets for organ specific metastasis of breast cancer; 2005-2010; $ 3,364,710
1. Peng H, Farrooji MTZ, Osborne MJ, Prokop JW, McDonald PC, Karar J, Hou Z, He M, Kebebew E, Orntoft T, Herlyn M, Caton AJ, Fredericks W, Malkowicz B, Paterno CS, Corolin AS, Speicher DW, Skordalakes E, Huang Q, Dedhar S, Borden KLB, Rauscher III, FJ. LIMD2 is a small LIM-only protein overexpressed in metastatic lesions which regulates cell motility and tumor progression by directly binding to and activating integrin-linked kinase. Cancer Res. 74, 1390-1402, 2014. PMID: 24590809
2. Serrano,I, McDonald,PC, Lock,F, Muller,W, and Dedhar, S. Inactivation of the Hippo tumor suppressor pathway by Integrin-Linked Kinase (ILK) Nature Communications. 4, 2976, 2013. PMID: 24356468
3. Kawamura E, Fielding AB, Kannan N, Balgi A, Eaves CJ, Roberge M, Dedhar S. Identification of novel small molecule inhibitors of centrosome clustering in cancer cells. Oncotarget. 2013 Oct;4(10):1763-76. PMID: 24091544
4. Lock FE, McDonald PC, Lou Y, Serrano I, Chafe SC, Ostlund C, Aparicio S, Winum JY, Supuran CT, Dedhar S. Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche. Oncogene. 2013 Oct 31;32(44):5210-9. PMID: 23208505
5. McDonald PC, Dedhar S. Carbonic Anhydrase IX (CAIX) as a Mediator of Hypoxia-Induced Stress Response in Cancer Cells. Subcell Biochem. 2014;75:255-69. PMID: 24146383
6. Barakat B, Yu L, Lo C, Vu D, De Luca E, Cain JE, Martellotto LG, Dedhar S, Sadler AJ, Wang D, Watkins DN, Hannigan GE. Interaction of smoothened with integrin-linked kinase in primary cilia mediates Hedgehog signalling. EMBO Rep. 2013 Sep;14(9):837-44. PMID: 23877428
7. Becker-Santos DD, Guo Y, Ghaffari M, Vickers ED, Lehman M, Altamirano-Dimas M, Oloumi A, Furukawa J, Sharma M, Wang Y, Dedhar S, Cox ME. Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models. Carcinogenesis. 2012 Dec;33(12):2558-67. PMID: 23027626
8. Serrano I, McDonald PC, Lock FE, Dedhar S. Role of the integrin-linked kinase (ILK)/Rictor complex in TGFβ-1-induced epithelial-mesenchymal transition (EMT). Oncogene. 2013 Jan 3;32(1):50-60. PMID: 22310280
9. Lou Y, McDonald PC, Oloumi A, Chia S, Ostlund C, Ahmadi A, Kyle A, Auf dem Keller U, Leung S, Huntsman D, Clarke B, Sutherland BW, Waterhouse D, Bally M, Roskelley C, Overall CM, Minchinton A, Pacchiano F, Carta F, Scozzafava A, Touisni N, Winum JY, Supuran CT, Dedhar S. Targeting tumor hypoxia: suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res. 2011 May 1;71(9):3364-76. PMID: 21415165
10. Pacchiano F, Carta F, McDonald PC, Lou Y, Vullo D, Scozzafava A, Dedhar S, Superan CT. Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis. J MED Chem 2011 Mar 24;54(6):1896-902. PMID: 21361354
11. Matsui Y, Assi K, Ogawa O, Raven PA, Dedhar S, Gleave ME, Salh B, So AI. The importantance of integrin-linked kinase in the regulation of bladder cancer invasion. Int J Cancer 2011 Feb 23.doi:10.1002/ijc.26008. (Epub ahead of print). PMID: 21355626
12. Perez VA, Ali Z, Alastalo TP, Ikeno F, Sawada H, Lai YJ, Kleisli T, Spiekerkoetter E, Qu X, Rubinos LH, Ashley E, Amieva E, Amieva M, Dedhar S, Rabinovitch M. BMP promotes motility and represses growth of smooth muscle cells by activiation of tandem Wnt pathways. J Cell Biol. 2011 Jan 10;192(1):171-88. PMID: 21220513
13. Faralli JA, Newman JR, Sheibani N, Dedhar S, Peters DM. Integrin-linked kinase regulates integrin signaling in human travecular meshwork cells. Invest Ophthalmol Vis Sci. 2011 Mar 25;52(3):1684-92. PMID: 21071740
14. Fielding AB, Lim S, Montgomery K, Dobreva I, Dedhar S.: A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells. Oncogene 2011 Feb 3;30(5):521-34. PMID: 20838383
15. Kalra J, Sutherland BW, Stratford AL, Dragowska W, Gelmon KA, Dedhar S, Dunn SE, Bally MB: Suppression of Her2/neu expression through ILK inhibition is regulated by a pathway involving TWIST and YB-1. Oncogene 2010 Dec 2;29(48):6343-56 PMID: 20838384
16. Maydan M, McDonald PC, Sanghera J, Yan J, Rallis C, Pinchin S, Hannigan GE, Foster LJ, Ish-Horowicz D, Walsh MP, Dedhar S.: Integrin-linkeed kinase is a functional Mn2+dependent protein kinase that regulates glycogen synthase kinase-3β (GSK-3beta) phosphorylation. PLoS One. 2010 Aug 23:5(8):e12356 PMID: 20827300
17. Auf dem Keller U, Bellac CL, Li Y, Lou Y, Lange PF, Ting R, Harwig C, Kappelhoff R, Dedhar S, Adam MJ, Ruth TJ, Benard F, Perrin DM, Overall CM.: Novel Matrix Metalloproteinase Inhibitor [18F] Marimastat-Aryltrifluoroborate as a Probe for In Vivo Positron Emission Tomography Imaging in Cancer. Cancer REs. 2010 Sept. 21 [Epub ahead of pring] PMID:20729277
18. Oloumi A, Maidan M, Lock FE, Terale H, McKinney S, Muller WJ, Aparicio SA, Dedhar S.: Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development. Breast Cancer Res. 2010;12(3):R38. Epub 2010 Jun 21 PMID 20565980
19. Pontier,SM, Huck, L, White DE, Rayment J, Sanguin-Gendreau V, Hennessy B, Zuo D, St-Arnaud R, Mills GB, Dedhar S, Marshall CJ, Muller WJ.: Integrin-linked kinase has a critical role in ErbB2 mamary tumor progression: implications for human breast cancer. Oncogene 2010 Jun 10;29(23):3374-85.
20. Dossa,T, Arabian,A., Dedhar, S, Teitelbaum.SI, Ross, P, Roodman,D, and St Arnaud,R. Osteoclast-specific inactivation of the Integrin-Linked Kinase (ILK) inhibits bone resorption. J. Cellular Biochem. 2010 Jul 1;110(4):960-7.
21. Muranyi AL, Dedhar S, Hogge DE. Targeting integrin linked kinase and FMS-like tyrosine kinase-3 is cytotoxic to acute myeloid leukemia stem cells but spares normal progenitors. Leuk Res 2010, in press.
22. Esfandiarei M, Yazdi SA, Gray V, Dedhar S, van Breemen C. Integrin-linked kinase functions as a downstream signal of platelet-derived growth factor to regulate actin polymerization and vascular smooth muscle cell migration. BMC Cell Biol 2010;11:16.
23. Muranyi AL, Dedhar S, Hogge DE. Combined inhibition of integrin linked kinase and FMS-like tyrosine kinase 3 is cytotoxic to acute myeloid leukemia progenitor cells. Exp Hematol 2009;37:450-60.
24. McDonald PC, Dedhar S, Keller C. Integrin-linked kinase: both Jekyll and Hyde in rhabdomyosarcoma. J Clin Invest 2009;119:1452-5.
25. Kalra J, Warburton C, Fang K, Edwards L, Daynard T, Waterhouse D, Dragowska W, Sutherland BW, Dedhar S, Gelmon K, Bally M. QLT0267, a small molecule inhibitor targeting integrin-linked kinase (ILK), and docetaxel can combine to produce synergistic interactions linked to enhanced cytotoxicity, reductions in P-AKT levels, altered F-actin architecture and improved treatment outcomes in an orthotopic breast cancer model. Breast Cancer Res 2009;11:R25.
26. Fielding AB, Dedhar S. The mitotic functions of integrin-linked kinase. Cancer Metastasis Rev 2009;28:99-111.
27. Akhtar N, Marlow R, Lambert E, Schatzmann F, Lowe ET, Cheung J, Katz E, Li W, Wu C, Dedhar S, Naylor MJ, Streuli CH. Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation. Development 2009;136:1019-27.
28. Tucker KL, Sage T, Stevens JM, Jordan PA, Jones S, Barrett NE, St-Arnaud R, Frampton J, Dedhar S, Gibbins JM. A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion. Blood 2008;112:4523-31.
29. Nakrieko KA, Welch I, Dupuis H, Bryce D, Pajak A, St Arnaud R, Dedhar S, D'Souza SJ, Dagnino L. Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis. Mol Biol Cell 2008;19:1462-73.
30. McPhee TR, McDonald PC, Oloumi A, Dedhar S. Integrin-linked kinase regulates E-cadherin expression through PARP-1. Dev Dyn 2008;237:2737-47.
31. McDonald PC, Oloumi A, Mills J, Dobreva I, Maidan M, Gray V, Wederell ED, Bally MB, Foster LJ, Dedhar S. Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival. Cancer Res 2008;68:1618-24.
32. McDonald PC, Fielding AB, Dedhar S. Integrin-linked kinase--essential roles in physiology and cancer biology. J Cell Sci 2008;121:3121-32.
33. Lou Y, Preobrazhenska O, auf dem Keller U, Sutcliffe M, Barclay L, McDonald PC, Roskelley C, Overall CM, Dedhar S. Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Dev Dyn 2008;237:2755-68.
34. Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, Stins MF, Wang X, Dedhar S, Lo EH. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci U S A 2008;105:7582-7.
35. Gkretsi V, Apte U, Mars WM, Bowen WC, Luo JH, Yang Y, Yu YP, Orr A, St-Arnaud R, Dedhar S, Kaestner KH, Wu C, Michalopoulos GK. Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly. Hepatology 2008;48:1932-41.
36. Fielding AB, Dobreva I, McDonald PC, Foster LJ, Dedhar S. Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization. J Cell Biol 2008;180:681-9.
37. Fielding AB, Dobreva I, Dedhar S. Beyond focal adhesions: integrin-linked kinase associates with tubulin and regulates mitotic spindle organization. Cell Cycle 2008;7:1899-906.
38. Edwards LA, Woo J, Huxham LA, Verreault M, Dragowska WH, Chiu G, Rajput A, Kyle AH, Kalra J, Yapp D, Yan H, Minchinton AI, Huntsman D, Daynard T, Waterhouse DN, Thiessen B, Dedhar S, Bally MB. Suppression of VEGF secretion and changes in glioblastoma multiforme microenvironment by inhibition of integrin-linked kinase (ILK). Mol Cancer Ther 2008;7:59-70.
39. Dobreva I, Fielding A, Foster LJ, Dedhar S. Mapping the integrin-linked kinase interactome using SILAC. J Proteome Res 2008;7:1740-9.
40. Assi K, Mills J, Owen D, Ong C, St Arnaud R, Dedhar S, Salh B. Integrin-linked kinase regulates cell proliferation and tumour growth in murine colitis-associated carcinogenesis. Gut 2008;57:931-40.
41. Wong RP, Ng P, Dedhar S, Li G. The role of integrin-linked kinase in melanoma cell migration, invasion, and tumor growth. Mol Cancer Ther 2007;6:1692-700.
42. Wang B, Li S, Dedhar S, Cleary PP. Paxillin phosphorylation: bifurcation point downstream of integrin-linked kinase (ILK) in streptococcal invasion. Cell Microbiol 2007;9:1519-28.
43. Li Y, Yang J, Luo JH, Dedhar S, Liu Y. Tubular epithelial cell dedifferentiation is driven by the helix-loop-helix transcriptional inhibitor Id1. J Am Soc Nephrol 2007;18:449-60.
44. Hannigan GE, Coles JG, Dedhar S. Integrin-linked kinase at the heart of cardiac contractility, repair, and disease. Circ Res 2007;100:1408-14.
45. Guo W, Jiang H, Gray V, Dedhar S, Rao Y. Role of the integrin-linked kinase (ILK) in determining neuronal polarity. Dev Biol 2007;306:457-68.
46. Gkretsi V, Mars WM, Bowen WC, Barua L, Yang Y, Guo L, St-Arnaud R, Dedhar S, Wu C, Michalopoulos GK. Loss of integrin linked kinase from mouse hepatocytes in vitro and in vivo results in apoptosis and hepatitis. Hepatology 2007;45:1025-34.
47. Gheyara AL, Vallejo-Illarramendi A, Zang K, Mei L, St-Arnaud R, Dedhar S, Reichardt LF. Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to alpha 7 beta 1-integrin deficiency. Am J Pathol 2007;171:1966-77.
48. Zhou FQ, Walzer M, Wu YH, Zhou J, Dedhar S, Snider WD. Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism. J Cell Sci 2006;119:2787-96.
49. White DE, Coutu P, Shi YF, Tardif JC, Nattel S, St Arnaud R, Dedhar S, Muller WJ. Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure. Genes Dev 2006;20:2355-60.
50. Waterhouse DN, Gelmon KA, Klasa R, Chi K, Huntsman D, Ramsay E, Wasan E, Edwards L, Tucker C, Zastre J, Wang YZ, Yapp D, Dragowska W, Dunn S, Dedhar S, Bally MB. Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers. Curr Cancer Drug Targets 2006;6:455-89.
51. Wang B, Yurecko RS, Dedhar S, Cleary PP. Integrin-linked kinase is an essential link between integrins and uptake of bacterial pathogens by epithelial cells. Cell Microbiol 2006;8:257-66.
52. Troussard AA, McDonald PC, Wederell ED, Mawji NM, Filipenko NR, Gelmon KA, Kucab JE, Dunn SE, Emerman JT, Bally MB, Dedhar S. Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival. Cancer Res 2006;66:393-403.
53. Rosano L, Spinella F, Di Castro V, Dedhar S, Nicotra MR, Natali PG, Bagnato A. Integrin-linked kinase functions as a downstream mediator of endothelin-1 to promote invasive behavior in ovarian carcinoma. Mol Cancer Ther 2006;5:833-42.
54. Oloumi A, Syam S, Dedhar S. Modulation of Wnt3a-mediated nuclear beta-catenin accumulation and activation by integrin-linked kinase in mammalian cells. Oncogene 2006;25:7747-57.
55. Naska S, Park KJ, Hannigan GE, Dedhar S, Miller FD, Kaplan DR. An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta pathway during dendrite initiation and growth. J Neurosci 2006;26:13344-56.
56. Mulholland DJ, Dedhar S, Wu H, Nelson CC. PTEN and GSK3beta: key regulators of progression to androgen-independent prostate cancer. Oncogene 2006;25:329-37.
57. Mills J, Niewmierzycka A, Oloumi A, Rico B, St-Arnaud R, Mackenzie IR, Mawji NM, Wilson J, Reichardt LF, Dedhar S. Critical role of integrin-linked kinase in granule cell precursor proliferation and cerebellar development. J Neurosci 2006;26:830-40.
58. Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 2006;172:973-81.
59. Esfandiarei M, Suarez A, Amaral A, Si X, Rahmani M, Dedhar S, McManus BM. Novel role for integrin-linked kinase in modulation of coxsackievirus B3 replication and virus-induced cardiomyocyte injury. Circ Res 2006;99:354-61.
60. El-Aouni C, Herbach N, Blattner SM, Henger A, Rastaldi MP, Jarad G, Miner JH, Moeller MJ, St-Arnaud R, Dedhar S, Holzman LB, Wanke R, Kretzler M. Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis. J Am Soc Nephrol 2006;17:1334-44.
61. Edwards LA, Verreault M, Thiessen B, Dragowska WH, Hu Y, Yeung JH, Dedhar S, Bally MB. Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells. Mol Cancer Ther 2006;5:645-54.
62. Dai C, Stolz DB, Bastacky SI, St-Arnaud R, Wu C, Dedhar S, Liu Y. Essential role of integrin-linked kinase in podocyte biology: Bridging the integrin and slit diaphragm signaling. J Am Soc Nephrol 2006;17:2164-75.
63. Bertram J, Peacock JW, Tan C, Mui AL, Chung SW, Gleave ME, Dedhar S, Cox ME, Ong CJ. Inhibition of the phosphatidylinositol 3'-kinase pathway promotes autocrine Fas-induced death of phosphatase and tensin homologue-deficient prostate cancer cells. Cancer Res 2006;66:4781-8.
64. Ahmed N, Maines-Bandiera S, Quinn MA, Unger WG, Dedhar S, Auersperg N. Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium. Am J Physiol Cell Physiol 2006;290:C1532-42.
65. Sutherland BW, Kucab J, Wu J, Lee C, Cheang MC, Yorida E, Turbin D, Dedhar S, Nelson C, Pollak M, Leighton Grimes H, Miller K, Badve S, Huntsman D, Blake-Gilks C, Chen M, Pallen CJ, Dunn SE. Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. Oncogene 2005;24:4281-92.
66. Rosano L, Spinella F, Di Castro V, Nicotra MR, Dedhar S, de Herreros AG, Natali PG, Bagnato A. Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells. Cancer Res 2005;65:11649-57.
67. Qian Y, Zhong X, Flynn DC, Zheng JZ, Qiao M, Wu C, Dedhar S, Shi X, Jiang BH. ILK mediates actin filament rearrangements and cell migration and invasion through PI3K/Akt/Rac1 signaling. Oncogene 2005;24:3154-65.
68. Niewmierzycka A, Mills J, St-Arnaud R, Dedhar S, Reichardt LF. Integrin-linked kinase deletion from mouse cortex results in cortical lamination defects resembling cobblestone lissencephaly. J Neurosci 2005;25:7022-31.
69. Mulholland DJ, Dedhar S, Coetzee GA, Nelson CC. Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Endocr Rev 2005;26:898-915.
70. Liu E, Sinha S, Williams C, Cyrille M, Heller E, Snapper SB, Georgopoulos K, St-Arnaud R, Force T, Dedhar S, Gerszten RE. Targeted deletion of integrin-linked kinase reveals a role in T-cell chemotaxis and survival. Mol Cell Biol 2005;25:11145-55.
71. Hannigan G, Troussard AA, Dedhar S. Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer 2005;5:51-63.
72. Filipenko NR, Attwell S, Roskelley C, Dedhar S. Integrin-linked kinase activity regulates Rac- and Cdc42-mediated actin cytoskeleton reorganization via alpha-PIX. Oncogene 2005;24:5837-49.
73. Edwards LA, Thiessen B, Dragowska WH, Daynard T, Bally MB, Dedhar S. Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth. Oncogene 2005;24:3596-605.
74. Chen H, Huang XN, Yan W, Chen K, Guo L, Tummalapali L, Dedhar S, St-Arnaud R, Wu C, Sepulveda JL. Role of the integrin-linked kinase/PINCH1/alpha-parvin complex in cardiac myocyte hypertrophy. Lab Invest 2005;85:1342-56.
75. Barker TH, Baneyx G, Cardo-Vila M, Workman GA, Weaver M, Menon PM, Dedhar S, Rempel SA, Arap W, Pasqualini R, Vogel V, Sage EH. SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity. J Biol Chem 2005;280:36483-93.
76. Zhou FQ, Zhou J, Dedhar S, Wu YH, Snider WD. NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. Neuron 2004;42:897-912.
77. Tan C, Cruet-Hennequart S, Troussard A, Fazli L, Costello P, Sutton K, Wheeler J, Gleave M, Sanghera J, Dedhar S. Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell 2004;5:79-90.
78. Quelo I, Gauthier C, Hannigan GE, Dedhar S, St-Arnaud R. Integrin-linked kinase regulates the nuclear entry of the c-Jun coactivator alpha-NAC and its coactivation potency. J Biol Chem 2004;279:43893-9.
79. Oloumi A, McPhee T, Dedhar S. Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim Biophys Acta 2004;1691:1-15.
80. McHardy LM, Sinotte R, Troussard A, Sheldon C, Church J, Williams DE, Andersen RJ, Dedhar S, Roberge M, Roskelley CD. The tumor invasion inhibitor dihydromotuporamine C activates RHO, remodels stress fibers and focal adhesions, and stimulates sodium-proton exchange. Cancer Res 2004;64:1468-74.
81. Friedrich EB, Liu E, Sinha S, Cook S, Milstone DS, MacRae CA, Mariotti M, Kuhlencordt PJ, Force T, Rosenzweig A, St-Arnaud R, Dedhar S, Gerszten RE. Integrin-linked kinase regulates endothelial cell survival and vascular development. Mol Cell Biol 2004;24:8134-44.
82. Edwards LA, Shabbits JA, Bally M, Dedhar S. Integrin-linked kinase (ILK) in combination molecular targeting. Cancer Treat Res 2004;119:59-75.
83. Barbera MJ, Puig I, Dominguez D, Julien-Grille S, Guaita-Esteruelas S, Peiro S, Baulida J, Franci C, Dedhar S, Larue L, Garcia de Herreros A. Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene 2004;23:7345-54.
84. Troussard AA, Mawji NM, Ong C, Mui A, St -Arnaud R, Dedhar S. Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation. J Biol Chem 2003;278:22374-8.
85. Terpstra L, Prud'homme J, Arabian A, Takeda S, Karsenty G, Dedhar S, St-Arnaud R. Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes. J Cell Biol 2003;162:139-48.
86. Persad S, Dedhar S. The role of integrin-linked kinase (ILK) in cancer progression. Cancer Metastasis Rev 2003;22:375-84.
87. Mills J, Digicaylioglu M, Legg AT, Young CE, Young SS, Barr AM, Fletcher L, O'Connor TP, Dedhar S. Role of integrin-linked kinase in nerve growth factor-stimulated neurite outgrowth. J Neurosci 2003;23:1638-48.
88. Marotta A, Parhar K, Owen D, Dedhar S, Salh B. Characterisation of integrin-linked kinase signalling in sporadic human colon cancer. Br J Cancer 2003;88:1755-62.
89. Cruet-Hennequart S, Maubant S, Luis J, Gauduchon P, Staedel C, Dedhar S. alpha(v) integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells. Oncogene 2003;22:1688-702.
90. Attwell S, Mills J, Troussard A, Wu C, Dedhar S. Integration of cell attachment, cytoskeletal localization, and signaling by integrin-linked kinase (ILK), CH-ILKBP, and the tumor suppressor PTEN. Mol Biol Cell 2003;14:4813-25.
91. Yoganathan N, Yee A, Zhang Z, Leung D, Yan J, Fazli L, Kojic DL, Costello PC, Jabali M, Dedhar S, Sanghera J. Integrin-linked kinase, a promising cancer therapeutic target: biochemical and biological properties. Pharmacol Ther 2002;93:233-42.
92. Tan C, Mui A, Dedhar S. Integrin-linked kinase regulates inducible nitric oxide synthase and cyclooxygenase-2 expression in an NF-kappa B-dependent manner. J Biol Chem 2002;277:3109-16.
93. Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J. Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem 2002;277:39209-16.
94. Friedrich EB, Sinha S, Li L, Dedhar S, Force T, Rosenzweig A, Gerszten RE. Role of integrin-linked kinase in leukocyte recruitment. J Biol Chem 2002;277:16371-5.
95. Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol 2001;155:505-10.
96. White DE, Cardiff RD, Dedhar S, Muller WJ. Mammary epithelial-specific expression of the integrin-linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice. Oncogene 2001;20:7064-72.
97. Tan C, Costello P, Sanghera J, Dominguez D, Baulida J, de Herreros AG, Dedhar S. Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells. Oncogene 2001;20:133-40.
98. Somasiri A, Howarth A, Goswami D, Dedhar S, Roskelley CD. Overexpression of the integrin-linked kinase mesenchymally transforms mammary epithelial cells. J Cell Sci 2001;114:1125-36.
99. Roskelley CD, Williams DE, McHardy LM, Leong KG, Troussard A, Karsan A, Andersen RJ, Dedhar S, Roberge M. Inhibition of tumor cell invasion and angiogenesis by motuporamines. Cancer Res 2001;61:6788-94.
100. Persad S, Troussard AA, McPhee TR, Mulholland DJ, Dedhar S. Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation. J Cell Biol 2001;153:1161-74.
101. Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J Biol Chem 2001;276:27462-9.
102. Mulholland DJ, Dedhar S, Vogl AW. Rat seminiferous epithelium contains a unique junction (Ectoplasmic specialization) with signaling properties both of cell/cell and cell/matrix junctions. Biol Reprod 2001;64:396-407.
103. Marotta A, Tan C, Gray V, Malik S, Gallinger S, Sanghera J, Dupuis B, Owen D, Dedhar S, Salh B. Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis. Oncogene 2001;20:6250-7.
104. Yoganathan TN, Costello P, Chen X, Jabali M, Yan J, Leung D, Zhang Z, Yee A, Dedhar S, Sanghera J. Integrin-linked kinase (ILK): a "hot" therapeutic target. Biochem Pharmacol 2000;60:1115-9.
105. Troussard AA, Costello P, Yoganathan TN, Kumagai S, Roskelley CD, Dedhar S. The integrin linked kinase (ILK) induces an invasive phenotype via AP-1 transcription factor-dependent upregulation of matrix metalloproteinase 9 (MMP-9). Oncogene 2000;19:5444-52.
106. Rauch F, Prud'homme J, Arabian A, Dedhar S, St-Arnaud R. Heart, brain, and body wall defects in mice lacking calreticulin. Exp Cell Res 2000;256:105-11.
107. Persad S, Attwell S, Gray V, Delcommenne M, Troussard A, Sanghera J, Dedhar S. Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells. Proc Natl Acad Sci U S A 2000;97:3207-12.
108. Dedhar S. Cell-substrate interactions and signaling through ILK. Curr Opin Cell Biol 2000;12:250-6.
109. D'Amico M, Hulit J, Amanatullah DF, Zafonte BT, Albanese C, Bouzahzah B, Fu M, Augenlicht LH, Donehower LA, Takemaru K, Moon RT, Davis R, Lisanti MP, Shtutman M, Zhurinsky J, Ben-Ze'ev A, Troussard AA, Dedhar S, Pestell RG. The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3beta and cAMP-responsive element-binding protein-dependent pathways. J Biol Chem 2000;275:32649-57.
110. Coppolino MG, Dedhar S. Bi-directional signal transduction by integrin receptors. Int J Biochem Cell Biol 2000;32:171-88.
111. Attwell S, Roskelley C, Dedhar S. The integrin-linked kinase (ILK) suppresses anoikis. Oncogene 2000;19:3811-5.
112. Troussard AA, Tan C, Yoganathan TN, Dedhar S. Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependent manner. Mol Cell Biol 1999;19:7420-7.
113. Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci 1999;56:523-37.
114. Downey GP, Dong Q, Kruger J, Dedhar S, Cherapanov V. Regulation of neutrophil activation in acute lung injury. Chest 1999;116:46S-54S.
115. Dedhar S, Williams B, Hannigan G. Integrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling. Trends Cell Biol 1999;9:319-23.
116. Dedhar S. Integrins and signal transduction. Curr Opin Hematol 1999;6:37-43.
117. Coppolino MG, Dedhar S. Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events. Biochem J 1999;340 ( Pt 1):41-50.
118. Wu C, Keightley SY, Leung-Hagesteijn C, Radeva G, Coppolino M, Goicoechea S, McDonald JA, Dedhar S. Integrin-linked protein kinase regulates fibronectin matrix assembly, E-cadherin expression, and tumorigenicity. J Biol Chem 1998;273:528-36.
119. Wang F, Weaver VM, Petersen OW, Larabell CA, Dedhar S, Briand P, Lupu R, Bissell MJ. Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc Natl Acad Sci U S A 1998;95:14821-6.
120. Novak A, Hsu SC, Leung-Hagesteijn C, Radeva G, Papkoff J, Montesano R, Roskelley C, Grosschedl R, Dedhar S. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways. Proc Natl Acad Sci U S A 1998;95:4374-9.
121. Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci U S A 1998;95:11211-6.
122. Coppolino MG, Dedhar S. Calreticulin. Int J Biochem Cell Biol 1998;30:553-8.
123. Shago M, Flock G, Leung Hagesteijn CY, Woodside M, Grinstein S, Giguere V, Dedhar S. Modulation of the retinoic acid and retinoid X receptor signaling pathways in P19 embryonal carcinoma cells by calreticulin. Exp Cell Res 1997;230:50-60.
124. Radeva G, Petrocelli T, Behrend E, Leung-Hagesteijn C, Filmus J, Slingerland J, Dedhar S. Overexpression of the integrin-linked kinase promotes anchorage-independent cell cycle progression. J Biol Chem 1997;272:13937-44.
125. Hannigan GE, Dedhar S. Protein kinase mediators of integrin signal transduction. J Mol Med 1997;75:35-44.
126. Hannigan GE, Bayani J, Weksberg R, Beatty B, Pandita A, Dedhar S, Squire J. Mapping of the gene encoding the integrin-linked kinase, ILK, to human chromosome 11p15.5-p15.4. Genomics 1997;42:177-9.
127. Coppolino MG, Woodside MJ, Demaurex N, Grinstein S, St-Arnaud R, Dedhar S. Calreticulin is essential for integrin-mediated calcium signalling and cell adhesion. Nature 1997;386:843-7.
128. St-Arnaud R, Candeliere GA, Dedhar S. New mechanisms of regulation of the genomic actions of vitamin D in bone cells: interaction of the vitamin D receptor with non-classical response elements and with the multifunctional protein, calreticulin. Front Biosci 1996;1:d177-88.
129. Kim YS, MacDonald PN, Dedhar S, Hruska KA. Association of 1 alpha,25-dihydroxyvitamin D3-occupied vitamin D receptors with cellular membrane acceptance sites. Endocrinology 1996;137:3649-58.
130. Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S. Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 1996;379:91-6.
131. Dedhar S, Hannigan GE. Integrin cytoplasmic interactions and bidirectional transmembrane signalling. Curr Opin Cell Biol 1996;8:657-69.
132. St-Arnaud R, Prud'homme J, Leung-Hagesteijn C, Dedhar S. Constitutive expression of calreticulin in osteoblasts inhibits mineralization. J Cell Biol 1995;131:1351-9.
133. Jewell K, Kapron-Bras C, Jeevaratnam P, Dedhar S. Stimulation of tyrosine phosphorylation of distinct proteins in response to antibody-mediated ligation and clustering of alpha 3 and alpha 6 integrins. J Cell Sci 1995;108 ( Pt 3):1165-74.
134. Demetriou M, Nabi IR, Coppolino M, Dedhar S, Dennis JW. Reduced contact-inhibition and substratum adhesion in epithelial cells expressing GlcNAc-transferase V. J Cell Biol 1995;130:383-92.
135. Dedhar S. Integrin mediated signal transduction in oncogenesis: an overview. Cancer Metastasis Rev 1995;14:165-72.
136. Coppolino M, Migliorini M, Argraves WS, Dedhar S. Identification of a novel form of the alpha 3 integrin subunit: covalent association with transferrin receptor. Biochem J 1995;306 ( Pt 1):129-34.
137. Coppolino M, Leung-Hagesteijn C, Dedhar S, Wilkins J. Inducible interaction of integrin alpha 2 beta 1 with calreticulin. Dependence on the activation state of the integrin. J Biol Chem 1995;270:23132-8.
138. Thacker JD, Dedhar S, Hogge DE. The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo. Int J Cancer 1994;56:236-43.
139. Leung-Hagesteijn CY, Milankov K, Michalak M, Wilkins J, Dedhar S. Cell attachment to extracellular matrix substrates is inhibited upon downregulation of expression of calreticulin, an intracellular integrin alpha-subunit-binding protein. J Cell Sci 1994;107 ( Pt 3):589-600.
140. Kruk PA, Uitto VJ, Firth JD, Dedhar S, Auersperg N. Reciprocal interactions between human ovarian surface epithelial cells and adjacent extracellular matrix. Exp Cell Res 1994;215:97-108.
141. Dedhar S, Rennie PS, Shago M, Hagesteijn CY, Yang H, Filmus J, Hawley RG, Bruchovsky N, Cheng H, Matusik RJ, et al. Inhibition of nuclear hormone receptor activity by calreticulin. Nature 1994;367:480-3.
142. Dedhar S. Novel functions for calreticulin: interaction with integrins and modulation of gene expression? Trends Biochem Sci 1994;19:269-71.
143. McGlade J, Brunkhorst B, Anderson D, Mbamalu G, Settleman J, Dedhar S, Rozakis-Adcock M, Chen LB, Pawson T. The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion. EMBO J 1993;12:3073-81.
144. Kapron-Bras C, Fitz-Gibbon L, Jeevaratnam P, Wilkins J, Dedhar S. Stimulation of tyrosine phosphorylation and accumulation of GTP-bound p21ras upon antibody-mediated alpha 2 beta 1 integrin activation in T-lymphoblastic cells. J Biol Chem 1993;268:20701-4.
145. Hughes DE, Salter DM, Dedhar S, Simpson R. Integrin expression in human bone. J Bone Miner Res 1993;8:527-33.
146. Dedhar S, Saulnier R, Nagle R, Overall CM. Specific alterations in the expression of alpha 3 beta 1 and alpha 6 beta 4 integrins in highly invasive and metastatic variants of human prostate carcinoma cells selected by in vitro invasion through reconstituted basement membrane. Clin Exp Metastasis 1993;11:391-400.
147. Lang LM, Gailey C, Myrdal SE, Dedhar S, Auersperg N. Divergence in patterns of invasion among subpopulations derived from a human carcinoma clone: roles of intercellular contacts and of cell-substratum adhesion. Tumour Biol 1992;13:364-77.
148. Dedhar S, Jewell K, Rojiani M, Gray V. The receptor for the basement membrane glycoprotein entactin is the integrin alpha 3/beta 1. J Biol Chem 1992;267:18908-14.
149. Dedhar S, Gray V, Robertson K, Saulnier R. Identification and characterization of a novel high-molecular-weight form of the integrin alpha 3 subunit. Exp Cell Res 1992;203:270-5.
150. Dedhar S, Eaves C. Effects of hematopoietic growth factors on nonhematopoietic cells. Immunol Ser 1992;57:601-14.
151. Rojiani MV, Finlay BB, Gray V, Dedhar S. In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. Biochemistry 1991;30:9859-66.
152. Finlay BB, Ruschkowski S, Dedhar S. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. J Cell Sci 1991;99 ( Pt 2):283-96.
153. Dedhar S, Robertson K, Gray V. Induction of expression of the alpha v beta 1 and alpha v beta 3 integrin heterodimers during retinoic acid-induced neuronal differentiation of murine embryonal carcinoma cells. J Biol Chem 1991;266:21846-52.
154. Akiyama H, Kawamata T, Dedhar S, McGeer PL. Immunohistochemical localization of vitronectin, its receptor and beta-3 integrin in Alzheimer brain tissue. J Neuroimmunol 1991;32:19-28.
155. Sutherland H, Dougherty G, Dedhar S. Developmental biology and oncology: two sides to the same coin? Sixth International Conference on the Differentiation of Normal and Neoplastic Cells sponsored by the International Society of Differentiation and the Canadian Society for Cellular and Molecular Biology, Vancouver, B.C., Canada, July 29-August 2, 1990. New Biol 1990;2:970-3.
156. McGeer PL, Zhu SG, Dedhar S. Immunostaining of human brain capillaries by antibodies to very late antigens. J Neuroimmunol 1990;26:213-8.
157. Lemoine FM, Dedhar S, Lima GM, Eaves CJ. Transformation-associated alterations in interactions between pre-B cells and fibronectin. Blood 1990;76:2311-20.
158. Dedhar S, Saulnier R. Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes. J Cell Biol 1990;110:481-9.
159. Dedhar S, Gray V. Isolation of a novel integrin receptor mediating Arg-Gly-Asp-directed cell adhesion to fibronectin and type I collagen from human neuroblastoma cells. Association of a novel beta 1-related subunit with alpha v. J Cell Biol 1990;110:2185-93.
160. Dedhar S. Integrins and tumor invasion. Bioessays 1990;12:583-90.
161. Klingemann HG, Dedhar S. Distribution of integrins on human peripheral blood mononuclear cells. Blood 1989;74:1348-54.
162. Dedhar S, Mitchell MD, Pierschbacher MD. The osteoblast-like differentiated phenotype of a variant of MG-63 osteosarcoma cell line correlated with altered adhesive properties. Connect Tissue Res 1989;20:49-61.
163. Dedhar S, Haqq C, Gray V. Specific overproduction of very late antigen 1 integrin in two human neuroblastoma cell lines selected for resistance to detachment by an Arg-Gly-Asp-containing synthetic peptide. J Biol Chem 1989;264:4832-6.
164. Dedhar S. Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1 beta in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity. J Cell Physiol 1989;138:291-9.
165. Dedhar S. Signal transduction via the beta 1 integrins is a required intermediate in interleukin-1 beta induction of alkaline phosphatase activity in human osteosarcoma cells. Exp Cell Res 1989;183:207-14.
166. Pierschbacher MD, Dedhar S, Ruoslahti E, Argraves S, Suzuki S. An adhesion variant of the MG-63 osteosarcoma cell line displays an osteoblast-like phenotype. Ciba Found Symp 1988;136:131-41.
167. Dedhar S, Gaboury L, Galloway P, Eaves C. Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. Proc Natl Acad Sci U S A 1988;85:9253-7.
168. Dedhar S, Ruoslahti E, Pierschbacher MD. A cell surface receptor complex for collagen type I recognizes the Arg-Gly-Asp sequence. J Cell Biol 1987;104:585-93.
169. Dedhar S, Argraves WS, Suzuki S, Ruoslahti E, Pierschbacher MD. Human osteosarcoma cells resistant to detachment by an Arg-Gly-Asp-containing peptide overproduce the fibronectin receptor. J Cell Biol 1987;105:1175-82.
170. Hill BT, Whelan RD, Goldie JH, Dedhar S. Methotrexate resistance in murine and human continuous tumour cell lines: an examination of the different mechanisms involved depending on the order of resistance expressed. Prog Clin Biol Res 1986;223:21-34.
171. Dedhar S, Freisheim JH, Hynes JB, Goldie JH. Further studies on substituted quinazolines and triazines as inhibitors of a methotrexate-insensitive murine dihydrofolate reductase. Biochem Pharmacol 1986;35:1143-7.
172. Dedhar S, Hartley D, Goldie JH. Increased dihydrofolate reductase activity in methotrexate-resistant human promyelocytic-leukaemia (HL-60) cells. Lack of correlation between increased activity and overproduction. Biochem J 1985;225:609-17.
173. Dedhar S, Hartley D, Fitz-Gibbons D, Phillips G, Goldie JH. Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients. J Clin Oncol 1985;3:1545-52.
174. Dedhar S, Goldie JH. Methotrexate-resistant human promyelocytic leukemia (HL-60) cells express a dihydrofolate reductase with altered properties associated with increased enzyme activity. Biochem Biophys Res Commun 1985;129:536-45.
175. Dedhar S, Goldie JH. Overproduction of two antigenically distinct forms of dihydrofolate reductase in a highly methotrexate-resistant mouse leukemia cell line. Cancer Res 1983;43:4863-71.
176. Dedhar S, Freisheim JH, Hynes JB, Goldie JH. Inhibition of a methotrexate-insensitive dihydrofolate reductase from L5178Y cells by substituted triazines and quinazolines. Biochem Pharmacol 1983;32:922-4.
177. Hill BT, Dedhar S, Goldie JH. Preliminary communications. Biochem Pharmacol 1982;31:263-6.
178. Goldie JH, Dedhar S, Krystal G. Properties of a methotrexate-insensitive variant of dihydrofolate reductase derived from methotrexate-resistant L5178Y cells. J Biol Chem 1981;256:11629-35.
179. Goldie JH, Krystal G, Hartley D, Gudauskas G, Dedhar S. A methotrexate insensitive variant of folate reductase present in two lines of methotrexate-resistant L5178Y cells. Eur J Cancer 1980;16:1539-46.
180. Tidd DM, Dedhar S. Specific and sensitive combined high-performance liquid chromatographic-flow fluorometric assay for intracellular 6-thioguanine nucleotides metabolites of 6-mercaptopurine and 6-thioguanine. J Chromatogr 1978;145:237-46.