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Int. J. Mol. Sci. 2014, 15(9), 15173-15187; doi:10.3390/ijms150915173

Curcumin Promotes KLF5 Proteasome Degradation through Downregulating YAP/TAZ in Bladder Cancer Cells

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Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
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Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China
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Author to whom correspondence should be addressed.
Received: 24 July 2014 / Revised: 13 August 2014 / Accepted: 20 August 2014 / Published: 28 August 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [3558 KB, uploaded 28 August 2014]   |  

Abstract

KLF5 (Krüppel-like factor 5) plays critical roles in normal and cancer cell proliferation through modulating cell cycle progression. In this study, we demonstrated that curcumin targeted KLF5 by promoting its proteasome degradation, but not by inhibiting its transcription in bladder cancer cells. We also demonstrated that lentivirus-based knockdown of KLF5 inhibited cancer cell growth, while over-expression of a Flag-tagged KLF5 could partially reverse the effects of curcumin on cell growth and cyclin D1 expression. Furthermore, we found that curcumin could down-regulate the expression of Hippo pathway effectors, YAP and TAZ, which have been reported to protect KLF5 protein from degradation. Indeed, knockdown of YAP by small interfering RNA caused the attenuation of KLF5 protein, but not KLF5 mRNA, which was reversed by co-incubation with proteasome inhibitor. A xenograft assay in nude mice finally proved the potent inhibitory effects of curcumin on tumor growth and the pro-proliferative YAP/TAZ/KLF5/cyclin D1 axis. Thus, our data indicates that curcumin promotes KLF5 proteasome-dependent degradation through targeting YAP/TAZ in bladder cancer cells and also suggests the therapeutic potential of curcumin in the treatment of bladder cancer. View Full-Text
Keywords: KLF5; curcumin; bladder cancer; protein degradation; YAP; TAZ KLF5; curcumin; bladder cancer; protein degradation; YAP; TAZ
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MDPI and ACS Style

Gao, Y.; Shi, Q.; Xu, S.; Du, C.; Liang, L.; Wu, K.; Wang, K.; Wang, X.; Chang, L.S.; He, D.; Guo, P. Curcumin Promotes KLF5 Proteasome Degradation through Downregulating YAP/TAZ in Bladder Cancer Cells. Int. J. Mol. Sci. 2014, 15, 15173-15187.

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