TAZ is overexpressed in prostate cancers and regulates the proliferation, migration and apoptosis of prostate cancer PC3 cells
TAZ is overexpressed in prostate cancers and regulates the proliferation, migration and apoptosis of prostate cancer PC3 cells
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DOI：
10.3892/or.2020.7616
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发表时间：
2020-08-01
期刊：
影响因子：
4.2
通讯作者：
Jiang, Shi-Wen
中科院分区：
文献类型：
--
作者：
Lin, Mengyuan;Bu, Chaozhi;Jiang, Shi-Wen
具有PDZ结合基序的转录共激活因子(转录共激活因子)，又称WW结构域转录调节因子1(WWTR1)，是HIPPO途径的下游效应因子，已被报道通过作为转录共激活因子来调控癌细胞的增殖、迁移和凋亡。然而，TAZ在前列腺癌细胞中的作用尚未被研究。本研究采用免疫组织化学方法检测了TAZ在前列腺癌(PCa)、良性前列腺增生症(BPH)组织、前列腺癌细胞系和正常前列腺上皮细胞中的表达。用shRNA敲除前列腺癌PC3细胞中的TAZ，并进行细胞存活率和迁移实验，以确定TAZ的生物学功能。采用小鼠异种皮下移植模型，研究了TAZ基因敲除对肿瘤生长的影响。我们发现TAZ在前列腺癌组织中过表达，并且其表达水平与肿瘤分级的Gleason评分呈正相关。此外，TAZ基因敲除抑制了PC3细胞的增殖，减少了细胞迁移，并诱导了细胞凋亡。进一步的实验证明，TAZ基因敲除可能通过诱导caspase-4和-7的表达和裂解，通过外源性的凋亡途径导致PC3细胞的凋亡。在肿瘤异种移植模型中，TAZ基因敲除导致肿瘤生长速度下降。综上所述，实验结果表明，TAZ在前列腺癌细胞的增殖、迁移和凋亡中起着重要的作用。TAZ可能是前列腺癌诊断和预后的有用生物标志物，并可能成为前列腺癌治疗的潜在靶点。
TAZ (transcriptional coactivator with PDZ-binding motif), which is also known as WW domain-containing transcription regulator 1 (WWTR1), a downstream effector of the Hippo pathway, has been reported to regulate cancer cell proliferation, migration and apoptosis by acting as a transcriptional coactivator. However, the function of TAZ in prostate cancer cells has not been investigated. In the present study, TAZ expression in prostate cancer (PCa) and benign prostatic hyperplasia tissues, PCa cell lines, and normal prostate epithelial cells was determined with the use of immunohistochemistry. TAZ was knocked down by shRNA in the PC3 cells, a prostate cancer cell line, and cell viability and migration assays were performed to determine the biological functions of TAZ. A mouse subcutaneous xenograft model was used to determine the in vivo effects of TAZ knockdown on tumor growth. We demonstrated that TAZ is overexpressed in PCa tissues, and the expression levels were found to be positively correlated with the Gleason scores of cancer grade. Moreover, TAZ knockdown inhibited PC3 cell proliferation, reduced cell migration, and induced apoptosis. Further experiments demonstrated that TAZ knockdown may lead to PC3 cell apoptosis through the exogenous apoptotic pathway by inducing the expression and cleavage of caspase-4 and -7. In the tumor xenograft model, TAZ knockdown led to a decreased tumor growth rate. Taken together, the experimental results indicate that TAZ plays a significant role in the proliferation, migration and apoptosis of prostate cancer cells. TAZ could be a useful biomarker for PCa diagnosis/prognosis, and it could be a potential target for the treatment of prostate cancers.