CSE1L Links cAMP/PKA and Ras/ERK pathways and regulates the expressions and phosphorylations of ERK1/2, CREB, and MITF in melanoma cells
Woan-Ruoh Lee
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorShing-Chuan Shen
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorPei-Ru Wu
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
Search for more papers by this authorChia-Lun Chou
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorYi-Hsien Shih
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorChung-Min Yeh
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
Search for more papers by this authorKun-Tu Yeh
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
School of Medicine, Chung Shan Medical University, Taichung, Taiwan
Search for more papers by this authorCorresponding Author
Ming-Chung Jiang
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Correspondence to: Department of Dermatology, School of Medicine, Taipei Medical University, No. 252 Wu-Hsing St Taipei 11031, Taiwan.
Search for more papers by this authorWoan-Ruoh Lee
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorShing-Chuan Shen
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorPei-Ru Wu
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
Search for more papers by this authorChia-Lun Chou
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorYi-Hsien Shih
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorChung-Min Yeh
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
Search for more papers by this authorKun-Tu Yeh
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
School of Medicine, Chung Shan Medical University, Taichung, Taiwan
Search for more papers by this authorCorresponding Author
Ming-Chung Jiang
Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Correspondence to: Department of Dermatology, School of Medicine, Taipei Medical University, No. 252 Wu-Hsing St Taipei 11031, Taiwan.
Search for more papers by this authorAbstract
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.
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