Document Detail


MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL.
MedLine Citation:
PMID:  23617806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The receptor tyrosine kinase AXL regulates melanoma cell proliferation and migration. We now demonstrate that AXL and the related kinase MERTK are alternately expressed in melanoma and are associated with different transcriptional signatures. MERTK-positive melanoma cells are more proliferative and less migratory than AXL-positive melanoma cells and overexpression of AXL increases cell motility relative to MERTK. MERTK is expressed in up to 50% of melanoma cells and shRNA-mediated knockdown of MERTK reduces colony formation and cell migration in a CDC42-dependent fashion. Targeting MERTK also decreases cell survival and proliferation in an AKT-dependent manner. Finally, we identify a novel mutation in the kinase domain of MERTK, MERTK(P) (802S) , that increases the motility of melanoma cells relative to wild-type MERTK. Together, these data demonstrate that MERTK is a possible therapeutic target in melanoma, that AXL and MERTK are associated with differential cell behaviors, and that mutations in MERTK may contribute to melanoma pathogenesis.
Authors:
Kathryn A Tworkoski; James T Platt; Antonella Bacchiocchi; Marcus Bosenberg; Titus J Boggon; David F Stern
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-05-21
Journal Detail:
Title:  Pigment cell & melanoma research     Volume:  26     ISSN:  1755-148X     ISO Abbreviation:  Pigment Cell Melanoma Res     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-26     Completed Date:  2014-02-06     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  101318927     Medline TA:  Pigment Cell Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  527-41     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Survival
Cytophotometry
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
HEK293 Cells
Humans
Melanoma / metabolism*
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
Phosphorylation
Proto-Oncogene Proteins / genetics,  metabolism*,  physiology*
Receptor Protein-Tyrosine Kinases / genetics,  metabolism*,  physiology*
Signal Transduction
Skin Neoplasms / metabolism
cdc42 GTP-Binding Protein / metabolism
Grant Support
ID/Acronym/Agency:
P50 CA121974/CA/NCI NIH HHS; P50 CA121974/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; EC 2.7.10.1/MERTK protein, human; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/axl receptor tyrosine kinase; EC 3.6.5.2/cdc42 GTP-Binding Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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