Document Detail

Aurora B is regulated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway and is a valuable potential target in melanoma cells.
MedLine Citation:
PMID:  22767597     Owner:  NLM     Status:  MEDLINE    
Metastatic melanoma is a deadly skin cancer and is resistant to almost all existing treatment. Vemurafenib, which targets the BRAFV600E mutation, is one of the drugs that improves patient outcome, but the patients next develop secondary resistance and a return to cancer. Thus, new therapeutic strategies are needed to treat melanomas and to increase the duration of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor response. The ERK pathway controls cell proliferation, and Aurora B plays a pivotal role in cell division. Here, we confirm that Aurora B is highly expressed in metastatic melanoma cells and that Aurora B inhibition triggers both senescence-like phenotypes and cell death in melanoma cells. Furthermore, we show that the BRAF/ERK axis controls Aurora B expression at the transcriptional level, likely through the transcription factor FOXM1. Our results provide insight into the mechanism of Aurora B regulation and the first molecular basis of Aurora B regulation in melanoma cells. The inhibition of Aurora B expression that we observed in vemurafenib-sensitive melanoma cells was rescued in cells resistant to this drug. Consistently, these latter cells remain sensitive to the effect of the Aurora B inhibitor. Noteworthy, wild-type BRAF melanoma cells are also sensitive to Aurora B inhibition. Collectively, our findings, showing that Aurora B is a potential target in melanoma cells, particularly in those vemurafenib-resistant, may open new avenues to improve the treatment of metastatic melanoma.
Caroline Bonet; Sandy Giuliano; Mickaël Ohanna; Karine Bille; Maryline Allegra; Jean-Philippe Lacour; Philippe Bahadoran; Stéphane Rocchi; Robert Ballotti; Corine Bertolotto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2012-11-19     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29887-98     Citation Subset:  IM    
Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et Pathologies des Mélanocytes de la Pigmentation Cutanée au Mélanome, Nice F-06204, France.
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MeSH Terms
Amino Acid Substitution
Cell Aging / drug effects,  genetics
Cell Death / drug effects,  genetics
Cell Division / drug effects,  genetics
Cell Line, Tumor
Drug Resistance, Neoplasm / drug effects,  genetics
Forkhead Transcription Factors / genetics,  metabolism
Gene Expression Regulation, Enzymologic*
Gene Expression Regulation, Neoplastic*
Indoles / pharmacology
MAP Kinase Signaling System*
Melanoma / enzymology*,  genetics,  pathology,  therapy
Mutation, Missense
Neoplasm Metastasis
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  biosynthesis*,  genetics
Proto-Oncogene Proteins B-raf / antagonists & inhibitors,  genetics,  metabolism
Skin Neoplasms / enzymology*,  genetics,  pathology,  therapy
Sulfonamides / pharmacology
Reg. No./Substance:
0/FOXM1 protein, human; 0/Forkhead Transcription Factors; 0/Foxm1 protein, mouse; 0/Indoles; 0/PLX4032; 0/Sulfonamides; EC protein, human; EC protein, mouse; EC Kinases; EC Proteins B-raf; EC kinase

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

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