Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner

Metformin was reported to inhibit the proliferation of many cancer cells, including melanoma cells. In this report, we investigated the effect of metformin on melanoma invasion and metastasis development. Using different in vitro approaches, we found that metformin inhibits cell invasion without aff...

Full description

Saved in:
Bibliographic Details
Published inMolecular cancer therapeutics Vol. 12; no. 8; pp. 1605 - 1615
Main Authors Cerezo, Michaël, Tichet, Mélanie, Abbe, Patricia, Ohanna, Mickaël, Lehraiki, Abdelali, Rouaud, Florian, Allegra, Maryline, Giacchero, Damien, Bahadoran, Philippe, Bertolotto, Corine, Tartare-Deckert, Sophie, Ballotti, Robert, Rocchi, Stéphane
Format Journal Article
LanguageEnglish
Published United States American Association for Cancer Research 01.08.2013
Subjects
AMP-Activated Protein Kinases - metabolism
Animals
Cancer
Cell Line, Tumor
Cell Movement - drug effects
Disease Models, Animal
Enzyme Activation - drug effects
Epithelial-Mesenchymal Transition - genetics
Female
Humans
Life Sciences
Melanoma - genetics
Melanoma - metabolism
Melanoma - pathology
Metalloendopeptidases - metabolism
Metformin - pharmacology
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Tumor Suppressor Protein p53 - metabolism
Online AccessGet full text

Cover

More Information
Summary:Metformin was reported to inhibit the proliferation of many cancer cells, including melanoma cells. In this report, we investigated the effect of metformin on melanoma invasion and metastasis development. Using different in vitro approaches, we found that metformin inhibits cell invasion without affecting cell migration and independently of antiproliferation action. This inhibition is correlated with modulation of expression of proteins involved in epithelial-mesenchymal transition such as Slug, Snail, SPARC, fibronectin, and N-cadherin and with inhibition of MMP-2 and MMP-9 activation. Furthermore, our data indicate that this process is dependent on activation of AMPK and tumor suppressor protein p53. Finally, we showed that metformin inhibits melanoma metastasis development in mice using extravasation and metastasis models. The presented data reinforce the fact that metformin might be a good candidate for clinical trial in melanoma treatment.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-12-1226-T