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Archives of Pharmacal Research

, Volume 42, Issue 6, pp 481–491 | Cite as

Targeting ROCK/LIMK/cofilin signaling pathway in cancer

  • Mee-Hyun Lee
  • Joydeb Kumar Kundu
  • Jung-Il Chae
  • Jung-Hyun ShimEmail author
Review
  • 311 Downloads

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.

Keywords

ROCK LIMK Cofilin Signaling pathways Inhibitors Cancer therapy 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

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Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Basic Medical CollegeZhengzhou UniversityZhengzhouChina
  2. 2.China-US (Henan) Hormel Cancer InstituteZhengzhouChina
  3. 3.Li Ka Shing Applied Virology InstituteUniversity of AlbertaEdmontonCanada
  4. 4.Department of Dental Pharmacology, School of Dentistry, BK21 PlusChonbuk National UniversityChonjuRepublic of Korea
  5. 5.Department of Pharmacy, College of PharmacyMokpo National UniversityMuanRepublic of Korea

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