Insig2 is associated with colon tumorigenesis and inhibits Bax-mediated apoptosis

Gong Li Chang, Mike Gruidl, Steven Eschrich, Susan McCarthy, Hong Gang Wang, Mark G. Alexandrow, Timothy J. Yeatman

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Insulin-induced gene 2 (Insig2) was recently identified as a putative positive prognostic biomarker for colon cancer prognosis. Insig2 has been previously reported to be an endoplasmic reticulum (ER) membrane protein, and a negative regulator of cholesterol synthesis. Here we report that Insig2 was validated as a gene with univariate negative prognostic capacity to discriminate human colon cancer survivorship. To investigate the functional roles it plays in tumor development and malignancy, Insig2 was over-expressed in colon cancer cells resulting in increased cellular proliferation, invasion, anchorage independent growth and inhibition of apoptosis. Over-expression of Insig2 appeared to suppress chemotherapeutic drug treatment-induced Bcl2 associated X protein (Bax) expression and activation. Insig2 was also found to localize to the mitochondria/heavy membrane fraction and associate with conformationally changed Bax. Moreover, Insig2 altered the expression of several additional apoptosis genes located in mitochondria, further supporting its new functional role in regulating mitochondrial mediated apoptosis. Our findings show that Insig2 is a novel colon cancer biomarker, and suggest, for the first time, a reasonable connection between Insig2 and Bax-mediated apoptosis through the mitochondrial pathway.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalInternational Journal of Cancer
Volume123
Issue number2
DOIs
StatePublished - Jul 15 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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