Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival.

The American Journal of Pathology
Sara E MeyerH Leighton Grimes

Abstract

K-RAS mutations are found in approximately 30% of lung cancers. The transcription factor Krüppel-like Factor 5 (KLF5) has been shown to mediate cellular transformation signaling events downstream of oncogenic RAS in other cancers, but a role for KLF5 in lung tumorigenesis has not been defined. We show here that knockdown of KLF5 expression significantly decreased anchorage-independent growth, but did not affect proliferation of human lung adenocarcinoma cells. Moreover, Klf5 is not required for lung tumor formation in an inducible oncogenic K-Ras(G12D) mouse model of lung tumorigenesis, and non-small cell lung cancer patients expressing high levels of KLF5 (21/258) have a significantly better disease-specific survival than those with intermediate to no KLF5 expression. Further, KLF5 knockdown in K-RAS-mutant human lung cancer cells resulted in a fivefold increase in ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2), an anthracycline drug transporter, which lead to significantly increased resistance to doxorubicin treatment, a chemotherapeutic agent clinically used to treat lung cancer. In summary, while KLF5 is not required for oncogenic mutant K-Ras-induced lung tumorigenesis, KLF5 regulation of ABCG2 expression may ...Continue Reading

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Citations

Dec 25, 2012·Yi chuan = Hereditas·Xin-Gang WuQian Huang
Feb 6, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiao-Jie LuShijie Ma
Jan 27, 2015·Journal of Physiology and Biochemistry·Yueling ZhangZhihe Zhao
Jul 14, 2019·Cancer Research·Hsi-Wen YehYuh-Shan Jou
Apr 4, 2021·Cancer Science·Yao Luo, Ceshi Chen

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