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 Academic Article uri icon

Overview

MeSH Major

  • Antigens, CD
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinoma, Renal Cell
  • Cell Adhesion Molecules
  • Genes, Neoplasm
  • Kidney Neoplasms
  • Neoplasm Proteins

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.

publication date

  • February 26, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3587206

Digital Object Identifier (DOI)

  • 10.1073/pnas.1222435110

PubMed ID

  • 23378636

Additional Document Info

start page

  • 3483

end page

  • 8

volume

  • 110

number

  • 9