Regulation of the potential marker for intestinal cells, Bmi1, by β-catenin and the zinc finger protein KLF4: Implications for colon cancer

Tianxin Yu, Xi Chen, Wen Zhang, Deannon Colon, Jiandang Shi, Dana Napier, Piotr Rychahou, Wange Lu, Eun Y. Lee, Heidi L. Weiss, B. Mark Evers, Chunming Liu

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

B lymphoma Mo-MLV insertion region 1 (Bmi1) is a Polycomb Group (PcG) protein important in gene silencing. It is a component of Polycomb Repressive Complex 1 (PRC1), which is required to maintain the transcriptionally repressive state of many genes. Bmi1 was initially identified as an oncogene that regulates cell proliferation and transformation, and is important in hematopoiesis and the development of nervous systems. Recently, it was reported that Bmi1 is a potential marker for intestinal stem cells. Because Wnt signaling plays a key role in intestinal stem cells, we analyzed the effects of Wnt signaling on Bmi1 expression.Wefound that Wnt signaling indeed regulates the expression of Bmi1 in colon cancer cells. In addition, the expression of Bmi1 in human colon cancers is significantly associated with nuclear β-catenin, a hallmark for the activated Wnt signaling. Krüppel-like factor 4 (KLF4) is a zinc finger protein highly expressed in the gut and skin. We recently found that KLF4 cross-talks with Wnt/β-catenin in regulating intestinal homeostasis. We demonstrated that KLF4 directly inhibits the expression of Bmi1 in colon cancer cells. We also found that Bmi1 regulates histone ubiquitination and is required for colon cancer proliferation in vitro and in vivo. Our findings further suggest that Bmi1 is an attractive target for cancer therapeutics.

Original languageEnglish
Pages (from-to)3760-3768
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number6
DOIs
StatePublished - Feb 3 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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