title: Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner.
abstract: 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.
authors.affiliation: Equipe Biologie et Pathologie des cellulesmelanocytaire: de la pigmentation cutanee au melanome, Centre Mediterraneen de Medecine Moleculaire (C3M), INSERM, U1065.
authors.forename: Michaël
authors.initials: M
authors.lastname: Cerezo
authors.forename: Mélanie
authors.initials: M
authors.lastname: Tichet
authors.forename: Patricia
authors.initials: P
authors.lastname: Abbe
authors.forename: Mickaël
authors.initials: M
authors.lastname: Ohanna
authors.forename: Abdelali
authors.initials: A
authors.lastname: Lehraiki
authors.forename: Florian
authors.initials: F
authors.lastname: Rouaud
authors.forename: Maryline
authors.initials: M
authors.lastname: Allegra
authors.forename: Damien
authors.initials: D
authors.lastname: Giacchero
authors.forename: Philippe
authors.initials: P
authors.lastname: Bahadoran
authors.forename: Corine
authors.initials: C
authors.lastname: Bertolotto
authors.forename: Sophie
authors.initials: S
authors.lastname: Tartare-Deckert
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rocchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008666:Metalloendopeptidases / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D008666:Metalloendopeptidases