Rho-associated protein kinase (ROCK) plays crucial roles in the proliferation and migration of different types of cells. ROCK inhibitor Y-27632 was previously reported to inhibit melanoma cell growth, and ROCK signaling was suggested to be a therapeutic target for treating melanoma. However, the negative effect of Y-27632 on melanoma cells was mainly seen in studies on murine B16 melanoma cells. Here, we reported that ROCK inhibitor actually promoted human melanoma cell growth and migration in vitro. Y-27632 increased the growth and migration of BRAF-mutated melanoma cells but had a negative effect on wild-type melanoma cells or primary melanocytes. We discovered that Y-27632 enhanced the growth of BRAF-mutated melanoma cells through increased ATK and ERK activity. The in vivo study further confirmed the in vitro finding. These data suggested that the effect of ROCK inhibitor on melanoma cells is cell-context dependent, and the application of ROCK inhibitor in the treatment of melanoma requires further study.
Keywords: AKT; BRAF; ERK; ROCK inhibitor; melanoma.
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.