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KLF8 transcription factor participates in oncogenic transformation

Abstract

Kruppel-like factor 8 (KLF8) is a member of the family of KLF transcription factors. Several KLF members have been shown to play a role in oncogenesis. We have previously demonstrated that KLF8 mediates cell cycle progression downstream of focal adhesion kinase (FAK) by upregulating cyclin D1. FAK plays a critical role in transformation and tumorigenesis and is aberrantly upregulated in many types of human cancer. Little is known about the function of KLF8 in these regards. Here we provide evidence suggesting a novel role of KLF8 in oncogenic transformation. We show that KLF8 expression is elevated in several types of human cancer cells and primary tumor tissues. Induced expression of ectopic KLF8 causes serum-independent growth and morphological transformation in NIH3T3 cells and enhances anchorage-independent growth of v-Src-transformed cells. In contrast, expression of a dominant-negative mutant of KLF8 dramatically suppresses the transformed phenotypes induced by v-Src. In addition, the KLF8-enhanced transformation in the v-Src cells was prevented by ablating cyclin D1 expression. Overall, these results indicate that KLF8 is required for v-Src-induced transformation and may play a role in tumor progression of human cancer.

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Acknowledgements

We thank Drs Jinsong Liu (T80) and Dihua Yu (SKOV3ip1) of the University of Texas, MD Anderson Cancer Center, Jin Q Cheng (SKOV3 and OVCAR5) of University of South Florida College of Medicine, C Michael DiPersio (MCF-7 and MDA-MB-231) and Gang Liu (MCF-10A) of our Center for kindly providing the cell lines. This work was supported by Albany Medical College Institutional Grant, Wendy Will Case Cancer Fund and American Cancer Society Grant (RSG CCG-111381) to JZ.

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Correspondence to J Zhao.

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Wang, X., Zhao, J. KLF8 transcription factor participates in oncogenic transformation. Oncogene 26, 456–461 (2007). https://doi.org/10.1038/sj.onc.1209796

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