In:
Molecular Carcinogenesis, Wiley, Vol. 55, No. 11 ( 2016-11), p. 1542-1552
Abstract:
The Ras/ERK (extracellular signal‐regulated protein kinase) and cAMP/PKA (protein kinase A) pathways are essential for the transcriptional activities of CREB (cAMP response element binding protein) and MITF (microphthalmia‐associated transcription factor) in melanogenesis and the progression of melanoma. However, the interaction between Ras/ERK and cAMP/PKA pathways in the melanogenesis and progression of melanoma is not fully known. Here, we report that CSE1L (chromosome segregation 1‐like protein) regulates cAMP/PKA‐induced CREB and MITF expressions as well as Ras‐induced ERK1/2 phosphorylation. IBMX, a cAMP/PKA activator, treatment induced CSE1L phosphorylation and augmented Ras‐induced ERK1/2 phosphorylation. CSE1L knockdown by CSE1L shRNA expression vectors inhibited Ras‐induced ERK1/2 phosphorylation and melanogenesis in melanoma cells. CSE1L overexpression increased phospho‐CREB expression; CSE1L knockdown also inhibited Ras‐induced phospho‐CREB, MITF, and tyrosinase expressions, regardless of the presence of IBMX. This study identifies CSE1L links and controls the Ras/ERK and cAMP/PKA pathways in the melanogenesis of melanoma cells. Melanomas frequently develop drug resistance via paradoxical activation of Ras/Raf/MEK/ERK or alternatively activated Ras/ERK and cAMP/PKA pathways. Thus CSE1L may be a potential target for treating melanomas that harbor Ras mutations or are resistant to drugs targeting Raf/MEK/ERK. © 2015 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0899-1987
,
1098-2744
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2001984-1
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