Human enhancer of filamentation 1 is a mediator of hypoxia-inducible factor-1α-mediated migration in colorectal carcinoma cells

Sun Hee Kim, Dianren Xia, Sang Wook Kim, Vijaykumar Holla, David G. Menter, Raymond N. DuBois

Research output: Contribution to journalArticle

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Abstract

Human enhancer of filamentation 1 (HEF1; also known as NEDD9 or Cas-L) is a scaffolding protein that is implicated in regulating diverse cellular processes, such as cellular attachment, motility, cell cycle progression, apoptosis, and inflammation. Here, we identify HEF1 as a novel hypoxia-inducible factor-1α (HIF-1α)-regulated gene and reveal that HEF1 mediates hypoxia-induced migration of colorectal carcinoma cells. HEF1 is highly expressed in cultured colorectal carcinoma cells exposed to hypoxia and in the hypoxic areas of human colorectal cancer (CRC) specimens. Moreover, our data show that HIF-1α mediates the effects of hypoxia on induction of HEF1 expression via binding to a hypoxia-responsive element of the HEF1 promoter. Importantly, the induction of HEF1 expression significantly enhances hypoxia-stimulated HIF-1α transcriptional activity by modulating the interaction between HIF-1α and its transcriptional cofactor p300. Inhibition of HEF1 expression also reduced the levels of hypoxia-inducible genes, including those that regulate cell motility. Cell migration was reduced dramatically following knockdown of HEF1 expression under hypoxic conditions. Thus, this positive feedback loop may contribute to adaptive responses of carcinoma cells encountering hypoxia during cancer progression.

Original languageEnglish (US)
Pages (from-to)4054-4063
Number of pages10
JournalCancer Research
Volume70
Issue number10
DOIs
StatePublished - May 15 2010
Externally publishedYes

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Hypoxia-Inducible Factor 1
Colorectal Neoplasms
Cell Movement
Cell Hypoxia
Genes
Hypoxia
Cell Cycle
Apoptosis
Inflammation
Carcinoma
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human enhancer of filamentation 1 is a mediator of hypoxia-inducible factor-1α-mediated migration in colorectal carcinoma cells. / Kim, Sun Hee; Xia, Dianren; Kim, Sang Wook; Holla, Vijaykumar; Menter, David G.; DuBois, Raymond N.

In: Cancer Research, Vol. 70, No. 10, 15.05.2010, p. 4054-4063.

Research output: Contribution to journalArticle

Kim, Sun Hee ; Xia, Dianren ; Kim, Sang Wook ; Holla, Vijaykumar ; Menter, David G. ; DuBois, Raymond N. / Human enhancer of filamentation 1 is a mediator of hypoxia-inducible factor-1α-mediated migration in colorectal carcinoma cells. In: Cancer Research. 2010 ; Vol. 70, No. 10. pp. 4054-4063.
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