PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling.
PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling.
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DOI：
10.1038/bjc.2011.384
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发表时间：
2011-10-25
影响因子：
8.8
通讯作者：
Campbell, F. C.
中科院分区：
文献类型：
--
作者：
Deevi, R.;Fatehullah, A.;Jagan, I.;Nagaraju, M.;Bingham, V.;Campbell, F. C.
10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)调节Rho样GTP酶CDc42在上皮极化生长中起着核心作用，但这个分子网络对细胞凋亡的影响尚不清楚。为了探讨CDC42在PTEN依赖的细胞死亡中的作用，我们采用了流式细胞术、体外下拉实验、多聚腺苷二磷酸核糖聚合酶(PARP)裂解和其他免疫印迹等方法对PTEN表达缺失的大肠细胞(HCT116PTEN+/+、HCT116PTEN−/−、CACO2和CACO2ShPTEN细胞)进行了转染或治疗策略的研究。流式细胞仪检测发现，PTEN基因敲除或被短发夹状RNA或小干扰RNA(SiRNA)抑制可抑制CDc42活性、PARP裂解和/或细胞凋亡。将野生型或有活性的CDC42导入细胞可促进PARP的切割，而沉默CDC42的siRNA可抑制PARP的切割和/或细胞凋亡。丁酸钠(NABT)对PTEN的药理作用增强了CDC42活性、PARP裂解和细胞凋亡，而CDC42siRNA则抑制了NABT诱导的PARP裂解。CDC42依赖的信号可以抑制糖原合成酶β(β)的活性。氯化锂对GSK_3β的药理抑制作用类似于Cd_(42)促进PARP裂解和/或细胞凋亡的作用。10号染色体上缺失的磷酸酶和张力蛋白同源物可能通过CDC42信号影响结直肠上皮细胞的凋亡，从而为极化生长和程序性细胞死亡提供了一个调控框架。
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) regulation of the Rho-like GTPase Cdc42 has a central role in epithelial polarised growth, but effects of this molecular network on apoptosis remain unclear. To investigate the role of Cdc42 in PTEN-dependent cell death, we used flow cytometry, in vitro pull-down assays, poly(ADP ribose) polymerase (PARP) cleavage and other immunoblots in isogenic PTEN-expressing and -deficient colorectal cells (HCT116PTEN+/+, HCT116PTEN−/−, Caco2 and Caco2 ShPTEN cells) after transfection or treatment strategies. The PTEN knockout or suppression by short hairpin RNA or small interfering RNA (siRNA) inhibited Cdc42 activity, PARP cleavage and/or apoptosis in flow cytometry assays. Transfection of cells with wild-type or constitutively active Cdc42 enhanced PARP cleavage, whereas siRNA silencing of Cdc42 inhibited PARP cleavage and/or apoptosis. Pharmacological upregulation of PTEN by sodium butyrate (NaBt) treatment enhanced Cdc42 activity, PARP cleavage and apoptosis, whereas Cdc42 siRNA suppressed NaBt-induced PARP cleavage. Cdc42-dependent signals can suppress glycogen synthase kinase-β (GSK3β) activity. Pharmacological inhibition of GSK3β by lithium chloride treatment mimicked effects of Cdc42 in promotion of PARP cleavage and/or apoptosis. Phosphatase and tensin homologue deleted on chromosome 10 may influence apoptosis in colorectal epithelium through Cdc42 signalling, thus providing a regulatory framework for both polarised growth and programmed cell death.
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影响因子：
4.8
作者：
El-Tanani, M;Platt-Higgins, A;Campbell, FC
通讯作者：
Campbell, FC
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
2.4
作者：
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通讯作者：
PARASKEVA, C
影响因子：
11.2
作者：
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通讯作者：
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影响因子：
6.2
作者：
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