HEF1 is a crucial mediator of the proliferative effects of prostaglandin E2 on colon cancer cells

Dianren Xia, Vijaykumar R. Holla, Dingzhi Wang, David G. Menter, Raymond N. DuBois

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2), one of the downstream products of cyclooxygenase-2 enzymatic activity, promotes colorectal carcinogenesis in part by stimulating cell division. In this study, we define a critical mechanism in this process by showing that the prometastatic adapter protein human enhancer of filamentation 1 (HEF1; NEDD9) links PGE2 to the cell cycle machinery in colorectal cancer cells. PGE2 rapidly induced expression of HEF1 mRNA and protein in colorectal cancer cells. HEF1 overexpression elicited the same effects as PGE2 treatment on cell proliferation, cell cycle progression, and tumor growth. Conversely, HEF1 knockdown suppressed PGE2-driven cell proliferation and cell cycle progression. Cell cycle alterations involved HEF1 fragmentation as well as co-distribution of HEF1 and cell cycle kinase Aurora A along spindle asters during cell division. Moreover, Aurora A co-immunoprecipitated with HEF1 and was activated by HEF1. Consistent with a role for HEF1 in colorectal carcinogenesis, we found elevated expression of HEF1 expression in 50% of human colorectal cancers examined, relative to paired normal tissues. These findings establish that PGE2 induces HEF1 expression, which in turn promotes cell cycle progression through its interaction with and activation of Aurora A. Further, they establish that HEF1 is a crucial downstream mediator of PGE 2 action during colorectal carcinogenesis.

Original languageEnglish (US)
Pages (from-to)824-831
Number of pages8
JournalCancer Research
Volume70
Issue number2
DOIs
StatePublished - Jan 15 2010
Externally publishedYes

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Dinoprostone
Colonic Neoplasms
Cell Cycle
Colorectal Neoplasms
Carcinogenesis
Cell Division
Aurora Kinase A
Cell Proliferation
Cyclooxygenase 2
Prostaglandins E
Messenger RNA
Growth
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

HEF1 is a crucial mediator of the proliferative effects of prostaglandin E2 on colon cancer cells. / Xia, Dianren; Holla, Vijaykumar R.; Wang, Dingzhi; Menter, David G.; DuBois, Raymond N.

In: Cancer Research, Vol. 70, No. 2, 15.01.2010, p. 824-831.

Research output: Contribution to journalArticle

Xia, Dianren ; Holla, Vijaykumar R. ; Wang, Dingzhi ; Menter, David G. ; DuBois, Raymond N. / HEF1 is a crucial mediator of the proliferative effects of prostaglandin E2 on colon cancer cells. In: Cancer Research. 2010 ; Vol. 70, No. 2. pp. 824-831.
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