Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity.
Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor, the expression of which is enriched in the postmitotic cells of the intestinal epithelium. KLF4 is a target gene of the tumor suppressor adenomatous polyposis coli (APC). We sought to determine the role of KLF4 in suppressing the tumorigenecity of RKO colon cancer cells, which do not express KLF4. We utilized an established system in RKO cells, in which an inducible promoter controls expression of KLF4. Four independent assays were used to assess the effects of KLF4 induction on tumor cells. We find that KLF4 overexpression reduces colony formation, cell migration and invasion, and in vivo tumorigenecity. The mechanism of action of KLF4 does not involve apoptosis. These findings, along with our previous findings that KLF4 induces G1/S arrest, suggest that KLF4 is a cell cycle checkpoint protein that can reduce tumorigenecity of colon cancer cells.
Dang
Duyen T
DT
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ddang@jhu.edu
Chen
Xinming
X
Feng
Jing
J
Torbenson
Michael
M
Dang
Long H
LH
Yang
Vincent W
VW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors