LIM Kinases: Role in cancer cytoskeleton remodelling and metastasis

LIM kinases (LIMK1 and LIMK2) are key serine/threonine kinases that regulate via phosphorylation and inactivation of cofilin, therefore affecting proliferation, cellular migration, and invasion. These proteins affect the stability of actin filaments, resulting in the promotion of cancer cell motility. This review comprehensively examines the molecular role in tumor dynamics, actin remodelling, motility, and the signalling functions of LIMKs in oncology highlighting their overexpression and functional dysregulation in multiple forms of cancer. Key oncogenic pathways-including Rho/ROCK, Rac1/Cdc42/PAK, PI3K/Akt, MAPK, and Hippo-YAP/TAZ-focus on LIMKs, reinforcing their importance as integrative signalling nodes. In silico mapping by STRING analysis reveals that LIMKs interact across multiple oncogenic and cytoskeletal regulators, forming a dense protein-protein interaction network, which confirms the functionally enriched and likely to be involved in common oncological processes. Furthermore, this review discusses the activity of LIMK isoforms across diverse cancers by identifying the biological effect and their mechanisms, therapeutic roles, and the small-molecule inhibitors of LIMKs with anti-metastatic potential. Overall, our review identifies LIMKs as potential molecular targets for developing anticancer therapeutics targeted at minimizing metastasis and increasing treatment efficacy.