A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma

Science Translational Medicine

Volumn 3, Issue 85, 2011, Pages

  Suwaki, Natsuko ^a,g   Vanhecke, Elsa ^a,h   Atkins, Katelyn M ^b   Graf, Manuela ^a   Swabey, Katherine ^a   Huang, Paul ^a   Schraml, Peter ^c   Moch, Holger ^c   Cassidy, Amy Mulick ^a   Brewer, Daniel ^a   Al Lazikani, Bissan ^a   Workman, Paul ^a   De Bono, Johann ^a   Kaye, Stan B ^a   Larkin, James ^d   Gore, Martin E ^d   Sawyers, Charles L ^e   Nelson, Peter ^f   Beer, Tomasz M ^b   Geng, Hao ^b   Gao, Lina ^b   Qian, David Z ^b   Alumkal, Joshi J ^b   Thomas, Gary ^b   Thomas, George V ^a,b   more..

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^d ROYAL MARSDEN HOSPITAL   (United Kingdom)

^e MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^f Fred Hutchinson Cancer Research Center   (United States)

^g UNIVERSITY OF OXFORD   (United Kingdom)

^h INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

DASATINIB; HYPOXIA INDUCIBLE FACTOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE 1B; VON HIPPEL LINDAU PROTEIN; PROTEIN KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; THIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER RESISTANCE; CONTROLLED STUDY; DRUG EFFECT; DRUG SENSITIVITY; DRUG TARGETING; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; KIDNEY CARCINOMA; MAJOR CLINICAL STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEOMICS; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; WILD TYPE; CELL PROLIFERATION; DRUG RESISTANCE; IMMUNOPRECIPITATION; IN VITRO STUDY; METABOLISM; TUMOR CELL LINE;

CARCINOMA, RENAL CELL; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; HUMANS; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; PROTEIN KINASE INHIBITORS; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1; PYRIMIDINES; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES; THIAZOLES; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 79957791781     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002004     Document Type: Article

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47. Acknowledgments: We thank C. W. Ryan, W. Y. Kim, K. Ellwood-Yen, M. Ashcroft, S. Mittnacth, I. K. Mellinghoff, J. T. Erler, and R. Dresbeck for helpful discussions; J. G. Braun for academic support; L. Iwai, N. Martin, C. Garcia, P. Clarke, S. Eccles, and J. Dukes for technical expertise; M. C. Costello for artwork; W. Kaelin [Howard Hughes Medical Institute (HHMI)] for the HIF- 1α and HIF-2α prolyl hydroxylase mutants; J. Massagué (HHMI) for the Src shRNA, chicken Src, and Src T388I mutant; M. Ohh for the 786-0 VHL-WT plasmid; M. Okada and S. Nada for the Csk plasmids; and T. Mori, S. McWeeney, and S. Mongue-Tchokote from the Biostatistics Shared Resource of the Knight Cancer Institute (National Cancer Institute P30 CA 069533). M.E.G. thanks the Royal Marsden Hospital foundation. Funding: K.M.A. is supported by National Research Service Award T32 GM71338 and award RMS1112 from the Radiological Society of North America. P.W. is supported by Cancer Research UK program grant C309/A8274 and is a Cancer Research UK Life Fellow. This study was supported by NIH grants DK37274, CA151564 (G.T.), 1KL2 RR024141 01 through OCTRI and UL1 RR024140 (J.J.A.), R01CA149253-01 (D.Z.Q.), P30 CA069533 13S5 through OHSU Knight Cancer Institute and the Pacific Northwest Prostate Specialized Programs of Research Excellence (G.V.T.), Knight Cancer Institute award (G.T.), VHL Family Alliance, STOP Cancer Foundation, Experimental Cancer Medicine Center network and the Institute of Cancer Research (G.V.T.). Author contributions: N.S., E.V., K.S., H.G., and D.Z.Q. performed the cellular and biochemical experiments; M.G. conducted the immunohistochemical assays; P.S. and H.M. performed and analyzed the survival correlations; B.A.-L., D.B., and A.M.C. performed the statistical analysis on the tissue microarray and network interaction map; P.H. conducted the proteomics experiments; P.H., B.A.-L., and P.N. analyzed the proteomics data; K.M.A. and G.T. performed the in vitro kinase assays; L.G. and J.J.A. performed ChIP experiments; M.E.G., J.L., S.B.K., J.D.-B., and T.M.B. provided clinical samples for analysis and clinical insight; N.S., E.V., K.M.A., G.T., C.L.S., and P.W. provided critical input into the overall research direction; G.V.T. directed the research and wrote the manuscript with input from all the co-authors. Competing interests: J.D.-B. has a paid consulting relationship with AstraZeneca. The other authors declare that they have no competing interests.