Abstract
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.
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Acknowledgements
We thank Leslie Metzger (Johns Hopkins Oncology Center Cell Imaging Core Facility), Boris Baibakov, and Olga Kovbasnjuk (Johns Hopkins Gastroenterology Confocal Facility) for assistance with FACS analysis and microscopy. This work is supported by the National Institutes of Health Grants DK59970 (DTD), DK52230, and CA84197 (VWY). DTD is a recipient of the Research Scholar Award from the American Gastroenterology Association and the Basic Research Award from the Glaxo Institute for Digestive Health. VWY is a recipient of the Georgia Cancer Coalition Distinguished Cancer Clinician Scientist Award.
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Dang, D., Chen, X., Feng, J. et al. Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity. Oncogene 22, 3424–3430 (2003). https://doi.org/10.1038/sj.onc.1206413
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DOI: https://doi.org/10.1038/sj.onc.1206413
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