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dc.contributor.authorEmerling, B. M.
dc.contributor.authorBenes, Cyril H.
dc.contributor.authorPoulogiannis, G.
dc.contributor.authorCourtney, K.
dc.contributor.authorLiu, H.
dc.contributor.authorChoo-Wing, R.
dc.contributor.authorBellinger, Gary
dc.contributor.authorTsukazawa, K. S.
dc.contributor.authorBrown, V.
dc.contributor.authorSignoretti, S.
dc.contributor.authorSoltoff, S. P.
dc.contributor.authorCantley, Lewis C.
dc.contributor.authorBell, Eric L.
dc.date.accessioned2013-09-09T18:16:17Z
dc.date.available2013-09-09T18:16:17Z
dc.date.issued2013-02
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/80378
dc.description.abstractCUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is highly expressed in stem cells and frequently overexpressed and tyrosine-phosphorylated in cancer. CDCP1 promotes cancer cell metastasis. However, the mechanisms that regulate CDCP1 are not well-defined. Here we show that hypoxia induces CDCP1 expression and tyrosine phosphorylation in hypoxia-inducible factor (HIF)-2α–, but not HIF-1α–, dependent fashion. shRNA knockdown of CDCP1 impairs cancer cell migration under hypoxic conditions, whereas overexpression of HIF-2α promotes the growth of tumor xenografts in association with enhanced CDCP1 expression and tyrosine phosphorylation. Immunohistochemistry analysis of tissue microarray samples from tumors of patients with clear cell renal cell carcinoma shows that increased CDCP1 expression correlates with decreased overall survival. Together, these data support a critical role for CDCP1 as a unique HIF-2α target gene involved in the regulation of cancer metastasis, and suggest that CDCP1 is a biomarker and potential therapeutic target for metastatic cancers.en_US
dc.description.sponsorshipAmerican Cancer Society (Grant PF-08215-01-TBE)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1222435110en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleIdentification of CDCP1 as a hypoxia-inducible factor 2  (HIF-2 ) target gene that is associated with survival in clear cell renal cell carcinoma patientsen_US
dc.typeArticleen_US
dc.identifier.citationEmerling, B. M., C. H. Benes, G. Poulogiannis, E. L. Bell, K. Courtney, H. Liu, R. Choo-Wing, et al. “Identification of CDCP1 as a hypoxia-inducible factor 2  (HIF-2 ) target gene that is associated with survival in clear cell renal cell carcinoma patients.” Proceedings of the National Academy of Sciences 110, no. 9 (February 26, 2013): 3483-3488.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentPaul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)en_US
dc.contributor.mitauthorBell, Eric L.en_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsEmerling, B. M.; Benes, C. H.; Poulogiannis, G.; Bell, E. L.; Courtney, K.; Liu, H.; Choo-Wing, R.; Bellinger, G.; Tsukazawa, K. S.; Brown, V.; Signoretti, S.; Soltoff, S. P.; Cantley, L. C.en_US
mit.licensePUBLISHER_POLICYen_US


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