Opposite regulation of epithelial-to-mesenchymal transition and cell invasiveness by periostin between prostate and bladder cancer cells
Opposite regulation of epithelial-to-mesenchymal transition and cell invasiveness by periostin between prostate and bladder cancer cells
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DOI：
10.3892/ijo.2011.997
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发表时间：
2011-06-01
影响因子：
5.2
通讯作者：
Inoue, Hirokazu
中科院分区：
文献类型：
--
作者：
Kim, Chul Jang;Sakamoto, Kanami;Inoue, Hirokazu
我们之前的研究表明，在人类膀胱癌组织中，periostin的表达下调，并且异位表达的periostin抑制膀胱癌细胞的侵袭性。然而，在研究的大多数其他人类癌症中，骨膜蛋白的表达促进细胞侵袭。本研究通过对膀胱癌和前列腺癌细胞系上皮-间质转化（EMT）和细胞侵袭性的研究，发现骨膜蛋白对上皮-间质转化（EMT）和细胞侵袭性的调控相反。在膀胱癌细胞中，Periostin上调E-cadherin的表达，而在前列腺癌细胞中下调E-cadherin的表达。骨膜蛋白抑制膀胱癌细胞的侵袭性，而促进前列腺癌细胞的侵袭性。E-cadherin负调节因子Snail在前列腺癌细胞中被periostin上调，而E-cadherin负调节因子Twist在膀胱癌细胞中被下调。在膀胱癌细胞中，骨膜的c端区足以发挥这些功能，而在前列腺癌细胞中则不具备。用siRNA敲低内源性蜗牛蛋白抑制表达骨膜蛋白的前列腺癌细胞的细胞侵袭性。在膀胱癌细胞中，Periostin抑制Akt磷酸化，而在前列腺癌细胞中则增强Akt磷酸化。Akt抑制剂可增加E-cadherin的表达，抑制Twist的表达和细胞侵袭性。这些结果表明，Akt信号在E-cadherin表达和骨膜蛋白通过Snail和Twist侵袭细胞的细胞类型依赖性调控中发挥作用。
We previously showed that periostin expression is downregulated in human bladder cancer tissues and that ectopic expression of periostin suppresses the invasiveness of bladder cancer cells. However, in most other human cancers studied, the expression of periostin promotes cell invasiveness. In the present study, we investigated the regulation of the epithelial-to-mesenchymal transition (EMT) and cell invasiveness by periostin in bladder and prostate cancer cell lines, and found opposite regulation of EMT and cell invasiveness by periostin. Periostin upregulated E-cadherin expression in bladder cancer cells but downregulated it in prostate cancer cells. Periostin suppressed cell invasiveness in bladder cancer cells but promoted it in prostate cancer cells. Snail, a negative regulator of E-cadherin, was upregulated by periostin in prostate cancer cells, while Twist, another negative regulator of E-cadherin, was downregulated in bladder cancer cells. The C-terminal region of periost in was sufficient for these functions in bladder cancer cells but not in prostate cancer cells. Knockdown of endogenous Snail by siRNA suppressed cell invasiveness in prostate cancer cells expressing periostin. Periostin also suppressed Akt phosphorylation in bladder cancer cells but enhanced it in prostate cancer cells. Treatment with Akt inhibitor increased E-cadherin expression and suppressed both Twist expression and cell invasiveness of bladder cancer cells. These results indicate that Akt signaling plays a role in the cell-type-dependent regulation of E-cadherin expression and cell invasiveness by periostin via Snail and Twist.