title: Regulation of the potential marker for intestinal cells, Bmi1, by β-catenin and the zinc finger protein KLF4: implications for colon cancer.
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. We found 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.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40506, USA.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Deannon
authors.initials: D
authors.lastname: Colon
authors.forename: Jiandang
authors.initials: J
authors.lastname: Shi
authors.forename: Dana
authors.initials: D
authors.lastname: Napier
authors.forename: Piotr
authors.initials: P
authors.lastname: Rychahou
authors.forename: Wange
authors.initials: W
authors.lastname: Lu
authors.forename: Eun Y
authors.initials: EY
authors.lastname: Lee
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D054875:Ubiquitination / Q000235:genetics; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D006657:Histones; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D051176:beta Catenin; D063150:Polycomb Repressive Complex 1