title: Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients.
abstract: 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.
authors: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors: Brooke M
authors: BM
authors: Emerling
authors: Cyril H
authors: CH
authors: Benes
authors: George
authors: G
authors: Poulogiannis
authors: Eric L
authors: EL
authors: Bell
authors: Kevin
authors: K
authors: Courtney
authors: Hui
authors: H
authors: Liu
authors: Rayman
authors: R
authors: Choo-Wing
authors: Gary
authors: G
authors: Bellinger
authors: Kazumi S
authors: KS
authors: Tsukazawa
authors: Victoria
authors: V
authors: Brown
authors: Sabina
authors: S
authors: Signoretti
authors: Stephen P
authors: SP
authors: Soltoff
authors: Lewis C
authors: LC
authors: Cantley
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D019061:src-Family Kinases; D000099162:Endothelial PAS Domain-Containing Protein 1; C432044:CDCP1 protein, human
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