ROCK1 promotes migration and invasion of non-small-cell lung cancer cells through the PTEN/PI3K/FAK pathway
ROCK1 promotes migration and invasion of non-small-cell lung cancer cells through the PTEN/PI3K/FAK pathway
复制标题
ROCK1通过PTEN/PI3K/FAK通路促进非小细胞肺癌细胞迁移和侵袭
DOI：
10.3892/ijo.2019.4864
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发表时间：
2019-10-01
影响因子：
5.2
通讯作者：
Zhang, Rong
中科院分区：
文献类型：
--
作者：
Hu, Changpeng;Zhou, Huyue;Zhang, Rong
Rho相关蛋白激酶1（ROCK 1）是ROCK家族的成员，在肿瘤的细胞迁移和侵袭中起重要作用。已经发现ROCK 1在几种类型的癌症中过表达。然而，ROCK 1在非小细胞肺癌（NSCLC）中的作用知之甚少。在本研究中，ROCK 1在NSCLC细胞和组织中过表达，并且与NSCLC患者的生存不良相关。随后，使用shRNA建立ROCK 1敲低NSCLC细胞系。在细胞单层划痕和Transwell试验中，ROCK 1敲低显著降低了细胞的迁移和侵袭能力。ROCK 1敲低也被发现显著抑制细胞粘附能力。此外，通过ROCK 1敲低抑制粘着斑激酶（FAK）的磷酸化，降低NSCLC细胞的迁移和侵袭能力。该机制研究揭示了ROCK 1通过抑制磷酸酶和张力蛋白同源物（PTEN）/磷酸肌醇3-激酶（PI 3 K）/FAK途径显著增强细胞迁移和侵袭。更重要的是，PTEN/PI 3 K/FAK通路的中断显著地挽救了由ROCK 1敲低介导的细胞迁移和侵袭的抑制。总之，这些结果表明ROCK 1通过抑制细胞粘附能力在细胞迁移和侵袭中发挥新的作用，并表明ROCK 1可能作为治疗NSCLC的治疗靶点。
Rho-associated protein kinase 1 (ROCK1), a member of the ROCK family, serves an important function in cell migration and invasion in neoplasms. ROCK1 has been found to be overexpressed in several types of cancers. However, the role of ROCK1 in non-small-cell lung cancer (NSCLC) is poorly understood. In the present study, ROCK1 was found to be overexpressed in NSCLC cells and tissues, and it was associated with poor survival of NSCLC patients. Subsequently, ROCK1 knockdown NSCLC cell lines were established using shRNA. ROCK1 knockdown significantly reduced the migration and invasion ability in the cell monolayer scratching and Transwell assays. ROCK1 knockdown was also found to markedly inhibit cell adhesion ability. Moreover, the phosphorylation of focal adhesion kinase (FAK) was inhibited by ROCK1 knockdown, reducing NSCLC cell migration and invasion ability. This mechanistic study revealed that ROCK1 significantly enhanced cell migration and invasion by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/FAK pathway. More importantly, the interruption of the PTEN/PI3K/FAK pathway markedly rescued the inhibition of cell migration and invasion mediated by ROCK1 knockdown. Taken together, these results suggest a novel role for ROCK1 in cell migration and invasion by inhibiting cell adhesion ability, and indicate that ROCK1 may be of value as a therapeutic target for the treatment of NSCLC.