Basic Medical College, Zhengzhou University, Zhengzhou, 450001, Henan, China.
China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China.
Arch Pharm Res. 2019 Jun;42(6):481-491. doi: 10.1007/s12272-019-01153-w. Epub 2019 Apr 27.
Rho-associated coiled-coil-containing protein kinase (ROCK)/Lin11, Isl-1 and Mec-3 kinase (LIMK)/cofilin-signaling cascades are stimulated by receptor tyrosine kinases, G protein-coupled receptors, integrins and its ligands, growth factors, hormones, fibronectin, collagen, and laminin. Activated signaling cascades can cause transit from normal cells to cancer cells by modulating actin/filament dynamics. In various cancers including breast, prostate, and colorectal cancers, high expression or activity of each cascade protein is significantly associated with poor survival rate of patients as well as aggressive metastasis. Silencing ROCK, LIMK, or cofilin can abrogate their activities and inhibit cancer cell growth, invasion, and metastasis. Therefore ROCK/LIMK/cofilin signaling proteins might be good candidates to develop cancer prevention strategies or therapeutics. Currently, netarsudil, a ROCK inhibitor, is only used in clinical patients for glaucoma or ocular hypertension, but not for cancer. In this review, we will discuss comprehensive ROCK/LIMK/cofilin signaling pathway in cancers and its inhibitors for developing cancer therapy.
Rho 相关卷曲螺旋蛋白激酶 (ROCK)/Lin11、Isl-1 和 Mec-3 激酶 (LIMK)/丝切蛋白信号通路被受体酪氨酸激酶、G 蛋白偶联受体、整合素及其配体、生长因子、激素、纤维连接蛋白、胶原蛋白和层粘连蛋白激活。激活的信号通路可以通过调节肌动蛋白/细丝动力学使正常细胞向癌细胞转化。在包括乳腺癌、前列腺癌和结直肠癌在内的各种癌症中，每个信号通路蛋白的高表达或高活性与患者的生存率低以及侵袭性转移显著相关。沉默 ROCK、LIMK 或丝切蛋白可以阻断它们的活性并抑制癌细胞的生长、侵袭和转移。因此，ROCK/LIMK/丝切蛋白信号蛋白可能是开发癌症预防策略或治疗方法的良好候选物。目前，ROCK 抑制剂奈他舒地尔仅用于治疗青光眼或高眼压的临床患者，而不适用于癌症。在这篇综述中，我们将讨论癌症中的 ROCK/LIMK/丝切蛋白信号通路及其抑制剂在癌症治疗方面的应用。
