Department of Pharmacy, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, P.R. China.
Int J Oncol. 2019 Oct;55(4):833-844. doi: 10.3892/ijo.2019.4864. Epub 2019 Aug 30.
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.
Rho 相关蛋白激酶 1(ROCK1)是 ROCK 家族的成员,在肿瘤细胞迁移和侵袭中发挥重要作用。研究发现 ROCK1 在多种类型的癌症中过表达。然而,ROCK1 在非小细胞肺癌(NSCLC)中的作用尚未完全阐明。本研究发现 ROCK1 在 NSCLC 细胞和组织中过表达,与 NSCLC 患者的不良预后相关。随后,使用 shRNA 建立了 ROCK1 敲低的 NSCLC 细胞系。细胞单层划痕和 Transwell 分析显示,ROCK1 敲低显著降低了迁移和侵袭能力。ROCK1 敲低还明显抑制了细胞黏附能力。此外,ROCK1 敲低抑制了粘着斑激酶(FAK)的磷酸化,从而降低了 NSCLC 细胞的迁移和侵袭能力。这项机制研究表明,ROCK1 通过抑制磷酸酶和张力蛋白同源物(PTEN)/磷脂酰肌醇 3-激酶(PI3K)/FAK 通路显著增强了细胞迁移和侵袭能力。更重要的是,PTEN/PI3K/FAK 通路的阻断显著挽救了 ROCK1 敲低介导的细胞迁移和侵袭抑制作用。综上所述,这些结果表明 ROCK1 通过抑制细胞黏附能力在细胞迁移和侵袭中发挥新的作用,并表明 ROCK1 可能作为治疗 NSCLC 的治疗靶点具有价值。