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, Shing Chuan Shen, Pei Ru Wu, Chia Lun Chou, Yi Hsien Shih, Chung Min Yeh, Kun Tu Yeh, Ming Chung Jiang

研究成果: 雜誌貢獻文章

11 引文 (Scopus)

摘要

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.

原文英語
期刊Molecular Carcinogenesis
DOIs
出版狀態已發佈 - 十一月 2016

指紋

Cellular Apoptosis Susceptibility Protein
Microphthalmia-Associated Transcription Factor
Cyclic AMP Response Element-Binding Protein
MAP Kinase Signaling System
Melanoma
Phosphorylation
1-Methyl-3-isobutylxanthine
Mitogen-Activated Protein Kinase Kinases
Monophenol Monooxygenase
Extracellular Signal-Regulated MAP Kinases
Drug Delivery Systems
Drug Resistance
Protein Kinases
Small Interfering RNA

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

引用此文

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title = "CSE1L Links cAMP/PKA and Ras/ERK pathways and regulates the expressions and phosphorylations of ERK1/2, CREB, and MITF in melanoma cells",
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.",
keywords = "CREB, CSE1L, ERK1/2, Melanoma, MITF, Ras",
author = "Lee, {Woan Ruoh} and Shen, {Shing Chuan} and Wu, {Pei Ru} and Chou, {Chia Lun} and Shih, {Yi Hsien} and Yeh, {Chung Min} and Yeh, {Kun Tu} and Jiang, {Ming Chung}",
year = "2016",
month = "11",
doi = "10.1002/mc.22407",
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journal = "Molecular Carcinogenesis",
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T1 - CSE1L Links cAMP/PKA and Ras/ERK pathways and regulates the expressions and phosphorylations of ERK1/2, CREB, and MITF in melanoma cells

AU - Lee, Woan Ruoh

AU - Shen, Shing Chuan

AU - Wu, Pei Ru

AU - Chou, Chia Lun

AU - Shih, Yi Hsien

AU - Yeh, Chung Min

AU - Yeh, Kun Tu

AU - Jiang, Ming Chung

PY - 2016/11

Y1 - 2016/11

N2 - 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.

AB - 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.

KW - CREB

KW - CSE1L

KW - ERK1/2

KW - Melanoma

KW - MITF

KW - Ras

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