title: Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype.
abstract: Here, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with melanoma-initiating cell features. The secretome of senescent melanoma cells induces a panel of 52 genes, involved in cell movement and cell/cell interaction, among which AXL and ALDH1A3 have been implicated in melanoma development. We found that the secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties. Collectively, the findings provide insights into how the secretome of melanoma cells entering senescence upon chemotherapy treatments increases the tumorigenicity of naïve melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse.
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome. Equipe labellisée Ligue 2013, Nice, F-06204, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Ohanna
authors.forename: Yann
authors.initials: Y
authors.lastname: Cheli
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonet
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Bonazzi
authors.forename: Marylin
authors.initials: M
authors.lastname: Allegra
authors.forename: Sandy
authors.initials: S
authors.lastname: Giuliano
authors.forename: Karine
authors.initials: K
authors.lastname: Bille
authors.forename: Philippe
authors.initials: P
authors.lastname: Bahadoran
authors.forename: Damien
authors.initials: D
authors.lastname: Giacchero
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Lacour
authors.forename: Glen M
authors.initials: GM
authors.lastname: Boyle
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Hayward
authors.forename: Corine
authors.initials: C
authors.lastname: Bertolotto
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human