The role of Rho-associated coiled-coil kinases (ROCK) in cancer.

Rho-associated coiled-coil kinases (ROCKs) regulate the actin cytoskeleton by controlling cellular functions such as cell contraction, migration and adhesion. Within the ROCK family, two highly homologous isoforms with overlapping functions exist: ROCK1 and ROCK2. The roles of ROCKs are context-dependent, varying by cell type and microenvironment and have been associated with a variety of diseases, including cancer. Increasing evidence correlates ROCK overexpression with cancer progression, metastasis and therapeutic resistance, while ROCK2 inhibition has demonstrated greater tumour inhibition. By regulating cytoskeletal dynamics and phosphorylating downstream effectors, the RhoA/ROCK2 signalling pathway orchestrates cellular processes including cytoskeletal reorganisation, cellular motility and mediating cell cycle progression with specific roles in the epithelial-mesenchymal transition (EMT), vascular mimicry (VM) and fibrosis. Crosstalk with neighbouring pathways further amplifies these oncogenic effects, but our understanding remains incomplete. This review discusses the role of Rho-associated coiled-coil kinases, ROCK2 in particular, in carcinogenesis.