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.
|
Authors | Xiuqing Li, Ruifang Wang, Junzhen Zhang, Shanshan Yang, Kaiyuan Ji, Bin Du, Xuexian Liu, Bo Liu, Shuhui Qi, Qiong Jia, Ruiwen Fan |
Journal | In vitro cellular & developmental biology. Animal
(In Vitro Cell Dev Biol Anim)
Vol. 55
Issue 6
Pg. 416-425
(Jun 2019)
ISSN: 1543-706X [Electronic] Germany |
PMID | 31069610
(Publication Type: Journal Article)
|
Chemical References |
- Creb1 protein, mouse
- Cyclic AMP Response Element-Binding Protein
- Melanins
- Monophenol Monooxygenase
- Cyclin-Dependent Kinase 5
- CDK5 protein, human
- Cdk5 protein, mouse
|
Topics |
- Animals
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Cyclic AMP Response Element-Binding Protein
(metabolism)
- Cyclin-Dependent Kinase 5
(genetics, metabolism)
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Humans
- Melanins
(biosynthesis)
- Melanoma, Experimental
(metabolism, pathology)
- Mice
- Monophenol Monooxygenase
(metabolism)
|