Oncotarget

Research Papers:

Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype.

Mickaël Ohanna, Yann Cheli, Caroline Bonet, Vanessa F Bonazzi, Marylin Allegra, Sandy Giuliano, Karine Bille, Philippe Bahadoran, Damien Giacchero, Jean Philippe Lacour, Glen M Boyle, Nicholas F Hayward, Corine Bertolotto and Robert Ballotti _

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Oncotarget. 2013; 4:2212-2224. https://doi.org/10.18632/oncotarget.1143

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Abstract

Mickaël Ohanna1,2,*, Yann Cheli1,2,*, Caroline Bonet1,2, Vanessa F Bonazzi4, Marylin Allegra1,3, Sandy Giuliano1,2, Karine Bille1,2, Philippe Bahadoran1,2,3, Damien Giacchero3, Jean Philippe Lacour2,3, Glen M Boyle4, Nicholas F Hayward4, Corine Bertolotto1,2,* and Robert Ballotti1,2,3,*.

1 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

2 Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France

3 Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France

4 Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia

* These authors equally contributed to the work

Correspondence:

Robert Ballotti, email:

Keywords: melanoma, senescence, secretome, STAT3

Received: June 30, 2013 Accepted: August 17, 2013 Published: August 19, 2013

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.


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