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
CUB 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 hyp...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/80378 |
| _version_ | 1811097588699496448 |
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| author | Emerling, B. M. Benes, Cyril H. Poulogiannis, G. Courtney, K. Liu, H. Choo-Wing, R. Bellinger, Gary Tsukazawa, K. S. Brown, V. Signoretti, S. Soltoff, S. P. Cantley, Lewis C. Bell, Eric L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Emerling, B. M. Benes, Cyril H. Poulogiannis, G. Courtney, K. Liu, H. Choo-Wing, R. Bellinger, Gary Tsukazawa, K. S. Brown, V. Signoretti, S. Soltoff, S. P. Cantley, Lewis C. Bell, Eric L. |
| author_sort | Emerling, B. M. |
| collection | MIT |
| description | CUB 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. |
| first_indexed | 2024-09-23T17:02:00Z |
| format | Article |
| id | mit-1721.1/80378 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:02:00Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/803782022-10-03T09:54:12Z 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 Emerling, B. M. Benes, Cyril H. Poulogiannis, G. Courtney, K. Liu, H. Choo-Wing, R. Bellinger, Gary Tsukazawa, K. S. Brown, V. Signoretti, S. Soltoff, S. P. Cantley, Lewis C. Bell, Eric L. Massachusetts Institute of Technology. Department of Biology Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology) Bell, Eric L. CUB 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. American Cancer Society (Grant PF-08215-01-TBE) 2013-09-09T18:16:17Z 2013-09-09T18:16:17Z 2013-02 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/80378 Emerling, 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 http://dx.doi.org/10.1073/pnas.1222435110 Proceedings of the National Academy of Sciences Article 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. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Emerling, B. M. Benes, Cyril H. Poulogiannis, G. Courtney, K. Liu, H. Choo-Wing, R. Bellinger, Gary Tsukazawa, K. S. Brown, V. Signoretti, S. Soltoff, S. P. Cantley, Lewis C. Bell, Eric L. 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://hdl.handle.net/1721.1/80378 |
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