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Targeting ROCK/LIMK/cofilin signaling pathway in cancer

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Abstract

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.

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Acknowledgements

This research was supported by Basic Science Research program through the NRF Funded by the Ministry of Education, Science and Technology (2019R1A2C1005899) and “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ013842)” Rural Development Administration, Republic of Korea.

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  1. Basic Medical College, Zhengzhou University, Zhengzhou, 450001, Henan, China

    Mee-Hyun Lee

  2. China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China

    Mee-Hyun Lee & Jung-Hyun Shim

  3. Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Joydeb Kumar Kundu

  4. Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Chonju, 54896, Republic of Korea

    Jung-Il Chae

  5. Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Jeonnam, 58554, Republic of Korea

    Jung-Hyun Shim

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Lee, MH., Kundu, J.K., Chae, JI. et al. Targeting ROCK/LIMK/cofilin signaling pathway in cancer. Arch. Pharm. Res. 42, 481–491 (2019). https://doi.org/10.1007/s12272-019-01153-w

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