TAZ promotes cell growth and inhibits Celastrol-induced cell apoptosis.
TAZ promotes cell growth and inhibits Celastrol-induced cell apoptosis.
复制标题
TAZ 促进细胞生长并抑制雷公藤红醇诱导的细胞凋亡
DOI：
10.1042/bsr20160135
复制
发表时间：
2016-10
影响因子：
4
通讯作者：
Xu N
中科院分区：
文献类型：
--
作者：
Wang S;Ma K;Chen L;Zhu H;Liang S;Liu M;Xu N
TAZ能促进细胞增殖，抑制celastrol诱导的细胞凋亡。上调B细胞淋巴瘤-2 （Bcl-2）、下调Bcl-2相关X蛋白（Bax）、激活磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B （Akt）通路可能是TAZ抗凋亡的机制。Hippo通路是一种高度保守的与生物发育相关的信号通路，已被证明与肿瘤的发生和进展密切相关。yes-associated protein （YAP）是Hippo通路的主要下游效应蛋白，是参与细胞增殖和存活的靶基因的转录激活因子。作为一种致癌基因，YAP可以促进细胞生长，抑制细胞凋亡。Hippo通路的另一个主要下游效应因子是具有pdz结合基序的转录共激活因子（TAZ），其与YAP的同源性接近60%。在本研究中，我们假设TAZ可能具有与YAP相似的功能。为了验证这一问题，我们分别在T-Rex-293和HEK293细胞中建立了诱导和稳定表达TAZ的系统。细胞生长曲线、集落形成实验和肿瘤异种移植物生长结果表明，过表达TAZ能促进细胞在体内和体外的生长。同时，我们发现上调TAZ的表达可以部分恢复celastrol诱导的细胞凋亡。诱导TAZ过表达可上调其靶基因ANKRD、CYR61、结缔组织生长因子（CTGF），增加B细胞淋巴瘤-2 （Bcl-2）表达，降低Bcl-2相关X蛋白（Bax）表达，激活磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B （Akt）通路，这可能是TAZ抗凋亡的机制。这些结果表明TAZ作为癌基因可能是细胞增殖和凋亡的关键调控因子。
TAZ could promote cell proliferation and inhibit Celastrol-induced cell apoptosis. Up-regulation of B-cell lymphoma-2 (Bcl-2), down-regulation of Bcl-2 associated X protein (Bax) and activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway may be the mechanism underlying anti-apoptosis of TAZ. Hippo pathway is a highly conservative signalling pathway related to the development of organisms, which has been demonstrated to be strongly linked to the tumorigenesis and tumour progression. As the major downstream effector of Hippo pathway, yes-associated protein (YAP), is a transcriptional activator of target genes that are involved in cell proliferation and survival. As an oncogene, YAP can promote cell growth and inhibit cell apoptosis. Another major downstream effector of Hippo pathway, transcriptional co-activators with PDZ-binding motif (TAZ), is nearly 60% homologous with YAP. In the present study, we assume that TAZ probably has the similar function to YAP. To test this issue, we established an inducible and a stable expression system of TAZ in T-Rex-293 and HEK293 cells respectively. The results of cell growth curves, colony formation assay and tumour xenograft growth showed that overexpression of TAZ could promote cell growth in vitro and in vivo. Meanwhile, we found that up-regulated expression of TAZ could partially restore Celastrol-induced cell apoptosis. Induced overexpression of TAZ could up-regulate its target genes including ankyrin repeat domain-containing protein (ANKRD), cysteine-rich 61 (CYR61) and connective tissue growth factor (CTGF), increase the expression of B-cell lymphoma-2 (Bcl-2), decrease the expression of Bcl-2 associated X protein (Bax) and activate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, which may be the mechanism underlying anti-apoptosis of TAZ. All these findings indicated that TAZ acts as an oncogene that could be a key regulator of cell proliferation and apoptosis.