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

In Vitro Cell Dev Biol Anim. 2019 Jun;55(6):416-425. doi: 10.1007/s11626-019-00343-6. Epub 2019 May 8.

Abstract

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.

Keywords: Cdk5; Melanoma; Migration; Phosphorated CREB (p-CREB); Proliferation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase 5 / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanins / biosynthesis*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Monophenol Monooxygenase / metabolism*

Substances

  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Melanins
  • Monophenol Monooxygenase
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human
  • Cdk5 protein, mouse