Induction of integrin β3 by sustained ERK activity promotes the invasiveness of TGFβ-induced mesenchymal tumor cells
Induction of integrin β3 by sustained ERK activity promotes the invasiveness of TGFβ-induced mesenchymal tumor cells
复制标题
DOI：
10.1016/j.canlet.2016.04.012
复制
发表时间：
2016-07-01
期刊：
影响因子：
9.7
通讯作者：
Cha, Hyuk-Jin
中科院分区：
文献类型：
--
作者：
Hong, Soon-Ki;Park, Jeong-Rak;Cha, Hyuk-Jin
整合素β 3在上皮间质转化（EMT）和耐药性中的作用强调了其在癌症转移和复发中的重要性。然而，整合素β 3独特表达的分子机制还不太清楚。在本报告中，我们证明了反复暴露于转化生长因子β（TGF β），一种有效的EMT诱导剂，显著增加了A549肺癌细胞中整合素β 3的表达，这些细胞具有不同的间质特性，如肌动蛋白丝重组和侵袭性。值得注意的是，整合素β 3的表达与癌细胞的侵袭和迁移有关，并且不是由Smad 4依赖性途径决定的，而是由间充质癌细胞中持续的ERK 1/2活性决定的。这些数据表明ERK 1/2在介导整合素β 3表达的非经典TGF β信号通路中起重要作用。因此，靶向MEK/ERK活性似乎是抑制EMT相关癌症进展的有希望的治疗方法，所述癌症进展可能发生在TGF β富集的微环境中，这将导致抑制整联蛋白β 3阳性癌细胞的转移潜力。(C)2016爱思唯尔爱尔兰有限公司版权所有。
The emerging roles of integrin beta 3 in the epithelial mesenchymal transition (EMT) and drug resistance underline its significance in cancer metastasis and recurrence. However, the molecular mechanism underlying the distinctive expression of integrin beta 3 is less understood. In the present report, we demonstrated that repetitive exposure to transforming growth factor beta (TGF beta), a potent inducer of the EMT, significantly increased the expression of integrin beta 3 in A549 lung cancer cells with distinct mesenchymal properties, such as actin filament reorganization and invasiveness. Notably, integrin beta 3 expression was associated to cancer cell invasion and migration, and was determined not by Smad4-dependent pathways but by sustained ERK1/2 activity in the mesenchymal cancer cells. These data suggest that ERK1/2 plays an important role in mediating non-canonical TGF beta signal pathways for integrin beta 3 expression. Therefore, the targeting of the MEK/ERK activity seems to be a promising therapeutic approach to suppressing EMT-associated cancer progression that potentially occurs in TGF beta-enriched microenvironments, which would lead to the suppression of the metastatic potential of integrin beta 3-positive cancer cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.