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Cyclin-dependent kinase 5 regulates proliferation, migration, tyrosinase activity, and melanin production in B16-F10 melanoma cells via the essential regulator p-CREB

Li, Xiuqing, Wang, Ruifang, Zhang, Junzhen, Yang, Shanshan, Ji, Kaiyuan, Du, Bin, Liu, Xuexian, Liu, Bo, Qi, Shuhui, Jia, Qiong, Fan, Ruiwen
In vitro cellular & developmental biology 2019 v.55 no.6 pp. 416-425
carcinogenesis, cell movement, cell proliferation, cyclin-dependent kinase, enzyme activity, enzyme inhibition, in vitro studies, integrins, melanin, melanocytes, melanoma, metastasis, risk, therapeutics
Melanoma is an aggressive cancer with increasing incidence and a growing lifetime risk that arises from normal melanocytes or their precursors. A thorough understanding of the molecular mechanism of melanomagenesis and melanoma biology is essential for the diagnosis, prognostication, and therapy of melanoma. Cyclin-dependent protein kinase 5 (Cdk5) is one of the proteins highly expressed in B16-F10 melanoma cells that controls melanoma cell motility, invasiveness, and metastatic spread and might be a promising novel therapeutic target. The effect of Cdk5 on proliferation and migration, which are important for carcinogenesis, has not been reported. In the current study, we found that siRNA-mediated knockdown of Cdk5 in B16-F10 melanoma cells inhibited melanoma cell proliferation through downregulation of the CaMK4-p-CREB pathway, inhibited migration through downregulation of p-CREB, integrin beta 1, and integrin beta 5, and also inhibited tyrosinase activity and melanin production through p-CREB-MITF regulation. The results indicate that Cdk5 controls melanoma development, with an essential regulatory role for p-CREB.