Targeting ROCK/LIMK/cofilin signaling pathway in cancer.
Mee-Hyun LeeJoydeb Kumar KunduJung-Il ChaeJung-Hyun ShimPublished in: Archives of pharmacal research (2019)
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.
Keyphrases
- papillary thyroid
- signaling pathway
- end stage renal disease
- cancer therapy
- squamous cell
- protein kinase
- newly diagnosed
- chronic kidney disease
- induced apoptosis
- ejection fraction
- prostate cancer
- childhood cancer
- blood pressure
- pi k akt
- prognostic factors
- epithelial mesenchymal transition
- squamous cell carcinoma
- cell proliferation
- lymph node metastasis
- small molecule
- binding protein
- cell cycle arrest
- patient reported outcomes
- oxidative stress
- tyrosine kinase
- patient reported
- cell migration
- wound healing
- optic nerve