CINP is a novel cofactor of KLF5 required for its role in the promotion of cell proliferation, survival and tumor growth.
CINP is a novel cofactor of KLF5 required for its role in the promotion of cell proliferation, survival and tumor growth.
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DOI：
10.1002/ijc.31908
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发表时间：
2019-02-01
影响因子：
6.4
通讯作者：
Dong JT
中科院分区：
文献类型：
--
作者：
Wu Q;Fu C;Li M;Li J;Li Z;Qi L;Ci X;Ma G;Gao A;Fu X;A J;An N;Liu M;Li Y;King JL;Fu L;Zhang B;Dong JT
KRüppel-like factor5(KLF5)抑制和促进肿瘤生长依赖于细胞环境。促进肿瘤的机制可能是有针对性的治疗。虽然KLF5的一些转录靶点已经被确定并与KLF5介导的肿瘤生长有关，但KLF5如何调控这些基因仍有待解决。在此，我们用免疫共沉淀(co-IP)和液质联用(LC-MS/MS)方法，对KLF5促进肿瘤生长的TSU-PR1膀胱癌细胞系进行了鉴定，以确定KLF5与KLF5相互作用的核蛋白对KLF5的S促肿瘤作用所必需的作用。LC-MS/MS在KLF5抗体沉淀的核蛋白中发现了122个潜在的KLF5结合蛋白，其中前9个候选蛋白是AHNAK、TFAM、HSDL2、HNRNPC、CINP、IST1、FBL、PABPC1和SNRNP40。SRB分析表明，沉默CINP对KLF5表达细胞的生长抑制作用最强，但对亲本TSU-PR1细胞没有影响。进一步的分析不仅证实了KLF5和CINP之间的物理相互作用，还表明CINP的敲除减弱了KLF5对细胞周期、细胞凋亡和肿瘤发生的影响。沉默CINP还减弱了KLF5对多种基因和信号通路的影响，包括细胞周期调节因子Cyclin D1和凋亡相关的Caspase 7。这些结果表明，CINP是KLF5的辅助因子，对促进肿瘤生长至关重要，KLF5-CINP相互作用可能成为抑制KLF5促进肿瘤生长的新的治疗靶点。
Krüppel-like factor 5 (KLF5) both suppresses and promotes tumor growth depending on cellular context. The mechanisms underlying tumor promotion could be targetable for therapy. Although a number of transcriptional targets of KLF5 have been identified and implicated in KLF5-mediated tumor growth, how KLF5 regulates these genes remains to be addressed. Here we performed co-immunoprecipitation (co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the TSU-Pr1 bladder cancer cell line, in which KLF5 is shown to promote tumor growth, to identify KLF5-interacting nuclear proteins that are necessary for KLF5’s tumor promoting function. LC-MS/MS revealed 122 potential KLF5 binding proteins in the nuclear proteins precipitated by the KLF5 antibody, and the top nine candidates included AHNAK, TFAM, HSDL2, HNRNPC, CINP, IST1, FBL, PABPC1, and SNRNP40. SRB assays of these 9 proteins indicated that silencing CINP had the most potent inhibitory effect on cell growth in KLF5-expressing cells but did not affect parental TSU-Pr1 cells. Further analyses not only confirmed the physical interaction between KLF5 and CINP, also demonstrated that knockdown of CINP attenuated the effects of KLF5 on cell cycle progression, apoptosis, and tumorigenesis. Silencing CINP also attenuated the effect of KLF5 on the expression of a number of genes and signaling pathways, including cell cycle regulator Cyclin D1 and apoptosis-related Caspase 7. These results suggest that CINP is a cofactor of KLF5 that is crucial for the promotion of tumor growth, and that the KLF5-CINP interaction could be a novel therapeutic target for inhibiting KLF5-promoted tumor growth.
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在前列腺癌细胞中，KLF5 乙酰化的中断可将其功能从肿瘤抑制因子转变为肿瘤促进因子。
影响因子：
6.4
作者：
Li, Xin;Zhang, Baotong;Wu, Qiao;Ci, Xinpei;Zhao, Ranran;Zhang, Zhiqian;Xia, Siyuan;Su, Dan;Chen, Jie;Ma, Gui;Fu, Liya;Dong, Jin-Tang
通讯作者：
Dong, Jin-Tang
影响因子：
4.8
作者：
Liu, Rong;Zheng, Han-Qiu;Chen, Ceshi
通讯作者：
Chen, Ceshi
影响因子：
11.2
作者：
McConnell BB;Bialkowska AB;Nandan MO;Ghaleb AM;Gordon FJ;Yang VW
通讯作者：
Yang VW
影响因子：
6.4
作者：
Guo, Peng;Dong, Xue-Yuan;Zhao, Ke-Wen;Sun, Xiaodong;Li, Qunna;Dong, Jin-Tang
通讯作者：
Dong, Jin-Tang
影响因子：
11.2
作者：
Farrugia MK;Vanderbilt DB;Salkeni MA;Ruppert JM
通讯作者：
Ruppert JM