title: Curcumin promotes KLF5 proteasome degradation through downregulating YAP/TAZ in bladder cancer cells.
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.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. gaoyangxjtu@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. sq_880702@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. shanhuxs@163.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. 125302400@163.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. panda1773@gmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. yidaiwujin@126.com.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. shishan_86@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. wangxinyang0929@163.com.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. changlukes@yahoo.com.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Chang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. dalinhexjtu@163.com.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. guopeng661@mail.xjtu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D056741:Cyclin D / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D056741:Cyclin D; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin