Targeting ROCK/LIMK/cofilin signaling pathway in cancer

被引：83

作者：

Lee, Mee-Hyun ^{[1
,2
]}

Kundu, Joydeb Kumar ^{[3
]}

Chae, Jung-Il ^{[4
]}

Shim, Jung-Hyun ^{[2
,5
]}

机构：

[1] Zhengzhou Univ, Basic Med Coll, Zhengzhou 450001, Henan, Peoples R China

[2] China US Henan Hormel Canc Inst, 127,Dongming Rd, Zhengzhou 450008, Henan, Peoples R China

[3] Univ Alberta, Li Ka Shing Appl Virol Inst, Edmonton, AB T6G 2R3, Canada

[4] Chonbuk Natl Univ, Plus BK21, Dept Dent Pharmacol, Sch Dent, Chonju 54896, South Korea

[5] Mokpo Natl Univ, Coll Pharm, Dept Pharm, Muan 58554, Jeonnam, South Korea

来源：

ARCHIVES OF PHARMACAL RESEARCH | 2019年 / 42卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

ROCK; LIMK; Cofilin; Signaling pathways; Inhibitors; Cancer therapy; LIM-KINASE; RHO-KINASE; BREAST-CANCER; FASUDIL SUPPRESSES; VASCULOGENIC MIMICRY; RHOA/ROCK PATHWAY; PROSTATE-CANCER; ACTIN DYNAMICS; CELL-MIGRATION; ROCK INHIBITOR;

D O I：

10.1007/s12272-019-01153-w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：481 / 491

页数：11

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