Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype
Identifieur interne : 004492 ( Main/Exploration ); précédent : 004491; suivant : 004493Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype
Auteurs : Mickaël Ohanna [France] ; Yann Cheli [France] ; Caroline Bonet [France] ; Vanessa F. Bonazzi [Australie] ; Marylin Allegra [France] ; Sandy Giuliano [France] ; Karine Bille [France] ; Philippe Bahadoran [France] ; Damien Giacchero [France] ; Jean Philippe Lacour [France] ; Glen M. Boyle [Australie] ; Nicholas F. Hayward [Australie] ; Corine Bertolotto [France] ; Robert Ballotti [France]Source :
- Oncotarget [ 1949-2553 ] ; 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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PubMed: 24344100
PubMed Central: 3926821
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Bonazzi</name><affiliation wicri:level="1"><nlm:aff id="A4"> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006</wicri:regionArea><wicri:noRegion>Brisbane 4006</wicri:noRegion></affiliation></author><author><name sortKey="Allegra, Marylin" sort="Allegra, Marylin" uniqKey="Allegra M" first="Marylin" last="Allegra">Marylin Allegra</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome. 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Equipe labellisée Ligue 2013, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome. 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Equipe labellisée Ligue 2013, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome. 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Equipe labellisée Ligue 2013, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Giacchero, Damien" sort="Giacchero, Damien" uniqKey="Giacchero D" first="Damien" last="Giacchero">Damien Giacchero</name><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Lacour, Jean Philippe" sort="Lacour, Jean Philippe" uniqKey="Lacour J" first="Jean Philippe" last="Lacour">Jean Philippe Lacour</name><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Boyle, Glen M" sort="Boyle, Glen M" uniqKey="Boyle G" first="Glen M" last="Boyle">Glen M. Boyle</name><affiliation wicri:level="1"><nlm:aff id="A4"> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006</wicri:regionArea><wicri:noRegion>Brisbane 4006</wicri:noRegion></affiliation></author><author><name sortKey="Hayward, Nicholas F" sort="Hayward, Nicholas F" uniqKey="Hayward N" first="Nicholas F" last="Hayward">Nicholas F. Hayward</name><affiliation wicri:level="1"><nlm:aff id="A4"> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006</wicri:regionArea><wicri:noRegion>Brisbane 4006</wicri:noRegion></affiliation></author><author><name sortKey="Bertolotto, Corine" sort="Bertolotto, Corine" uniqKey="Bertolotto C" first="Corine" last="Bertolotto">Corine Bertolotto</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24344100</idno><idno type="pmc">3926821</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926821</idno><idno type="RBID">PMC:3926821</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002826</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002826</idno><idno type="wicri:Area/Pmc/Curation">002676</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002676</idno><idno type="wicri:Area/Pmc/Checkpoint">001890</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001890</idno><idno type="wicri:Area/Ncbi/Merge">001659</idno><idno type="wicri:Area/Ncbi/Curation">001659</idno><idno type="wicri:Area/Ncbi/Checkpoint">001659</idno><idno type="wicri:Area/Main/Merge">004578</idno><idno type="wicri:Area/Main/Curation">004492</idno><idno type="wicri:Area/Main/Exploration">004492</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype</title><author><name sortKey="Ohanna, Mickael" sort="Ohanna, Mickael" uniqKey="Ohanna M" first="Mickaël" last="Ohanna">Mickaël Ohanna</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Cheli, Yann" sort="Cheli, Yann" uniqKey="Cheli Y" first="Yann" last="Cheli">Yann Cheli</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Bonet, Caroline" sort="Bonet, Caroline" uniqKey="Bonet C" first="Caroline" last="Bonet">Caroline Bonet</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Bonazzi, Vanessa F" sort="Bonazzi, Vanessa F" uniqKey="Bonazzi V" first="Vanessa F" last="Bonazzi">Vanessa F. Bonazzi</name><affiliation wicri:level="1"><nlm:aff id="A4"> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006</wicri:regionArea><wicri:noRegion>Brisbane 4006</wicri:noRegion></affiliation></author><author><name sortKey="Allegra, Marylin" sort="Allegra, Marylin" uniqKey="Allegra M" first="Marylin" last="Allegra">Marylin Allegra</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Giuliano, Sandy" sort="Giuliano, Sandy" uniqKey="Giuliano S" first="Sandy" last="Giuliano">Sandy Giuliano</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Bille, Karine" sort="Bille, Karine" uniqKey="Bille K" first="Karine" last="Bille">Karine Bille</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Bahadoran, Philippe" sort="Bahadoran, Philippe" uniqKey="Bahadoran P" first="Philippe" last="Bahadoran">Philippe Bahadoran</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Giacchero, Damien" sort="Giacchero, Damien" uniqKey="Giacchero D" first="Damien" last="Giacchero">Damien Giacchero</name><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Lacour, Jean Philippe" sort="Lacour, Jean Philippe" uniqKey="Lacour J" first="Jean Philippe" last="Lacour">Jean Philippe Lacour</name><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author><author><name sortKey="Boyle, Glen M" sort="Boyle, Glen M" uniqKey="Boyle G" first="Glen M" last="Boyle">Glen M. Boyle</name><affiliation wicri:level="1"><nlm:aff id="A4"> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006</wicri:regionArea><wicri:noRegion>Brisbane 4006</wicri:noRegion></affiliation></author><author><name sortKey="Hayward, Nicholas F" sort="Hayward, Nicholas F" uniqKey="Hayward N" first="Nicholas F" last="Hayward">Nicholas F. Hayward</name><affiliation wicri:level="1"><nlm:aff id="A4"> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006</wicri:regionArea><wicri:noRegion>Brisbane 4006</wicri:noRegion></affiliation></author><author><name sortKey="Bertolotto, Corine" sort="Bertolotto, Corine" uniqKey="Bertolotto C" first="Corine" last="Bertolotto">Corine Bertolotto</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation></author><author><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name><affiliation wicri:level="1"><nlm:aff id="A1"> 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</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> 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</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Université de Nice Sophia-Antipolis, UFR Médecine, Nice, F-06107</wicri:regionArea><wicri:noRegion>06107</wicri:noRegion><wicri:noRegion>06107</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204</wicri:regionArea><wicri:noRegion>06204</wicri:noRegion><wicri:noRegion>06204</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Orgaz, Jl" uniqKey="Orgaz J">JL Orgaz</name></author><author><name sortKey="Sanz Moreno, V" uniqKey="Sanz Moreno V">V Sanz-Moreno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tawbi, Ha" uniqKey="Tawbi H">HA Tawbi</name></author><author><name sortKey="Buch, Sc" uniqKey="Buch S">SC Buch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheli, Y" uniqKey="Cheli Y">Y Cheli</name></author><author><name sortKey="Giuliano, S" uniqKey="Giuliano S">S Giuliano</name></author><author><name sortKey="Botton, T" 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Byers</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Nilsson, Mb" uniqKey="Nilsson M">MB Nilsson</name></author><author><name sortKey="Fujimoto, J" uniqKey="Fujimoto J">J Fujimoto</name></author><author><name sortKey="Saintigny, P" uniqKey="Saintigny P">P Saintigny</name></author><author><name sortKey="Yordy, J" uniqKey="Yordy J">J Yordy</name></author><author><name sortKey="Giri, U" uniqKey="Giri U">U Giri</name></author><author><name sortKey="Peyton, M" uniqKey="Peyton M">M Peyton</name></author><author><name sortKey="Fan, Yh" uniqKey="Fan Y">YH Fan</name></author><author><name sortKey="Diao, L" uniqKey="Diao L">L Diao</name></author><author><name sortKey="Masrorpour, F" uniqKey="Masrorpour F">F Masrorpour</name></author><author><name sortKey="Shen, L" uniqKey="Shen L">L Shen</name></author><author><name sortKey="Liu, W" uniqKey="Liu W">W Liu</name></author><author><name sortKey="Duchemann, B" uniqKey="Duchemann B">B Duchemann</name></author><author><name sortKey="Tumula, P" uniqKey="Tumula P">P Tumula</name></author><author><name sortKey="Bhardwaj, V" uniqKey="Bhardwaj V">V Bhardwaj</name></author><author><name sortKey="Welsh, J" uniqKey="Welsh J">J Welsh</name></author><author><name sortKey="Weber, S" uniqKey="Weber S">S Weber</name></author><author><name sortKey="Glisson, Bs" uniqKey="Glisson B">BS Glisson</name></author><author><name sortKey="Kalhor, N" uniqKey="Kalhor N">N Kalhor</name></author><author><name sortKey="Wistuba, Ii" uniqKey="Wistuba I">II Wistuba</name></author><author><name sortKey="Girard, L" uniqKey="Girard L">L Girard</name></author><author><name sortKey="Lippman, Sm" uniqKey="Lippman S">SM Lippman</name></author><author><name sortKey="Mills, Gb" uniqKey="Mills G">GB Mills</name></author><author><name sortKey="Coombes, Kr" uniqKey="Coombes K">KR Coombes</name></author><author><name sortKey="Weinstein, Jn" uniqKey="Weinstein J">JN Weinstein</name></author><author><name sortKey="Minna, Jd" uniqKey="Minna J">JD Minna</name></author><author><name sortKey="Heymach, Jv" uniqKey="Heymach J">JV Heymach</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sensi, M" uniqKey="Sensi M">M Sensi</name></author><author><name sortKey="Catani, M" uniqKey="Catani M">M Catani</name></author><author><name sortKey="Castellano, G" uniqKey="Castellano G">G Castellano</name></author><author><name sortKey="Nicolini, G" uniqKey="Nicolini G">G Nicolini</name></author><author><name sortKey="Alciato, F" uniqKey="Alciato F">F Alciato</name></author><author><name sortKey="Tragni, G" uniqKey="Tragni G">G Tragni</name></author><author><name sortKey="De Santis, G" uniqKey="De Santis G">G De Santis</name></author><author><name sortKey="Bersani, I" uniqKey="Bersani I">I Bersani</name></author><author><name sortKey="Avanzi, G" uniqKey="Avanzi G">G Avanzi</name></author><author><name sortKey="Tomassetti, A" uniqKey="Tomassetti A">A Tomassetti</name></author><author><name sortKey="Canevari, S" uniqKey="Canevari S">S Canevari</name></author><author><name sortKey="Anichini, A" uniqKey="Anichini A">A Anichini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Y" uniqKey="Tang Y">Y Tang</name></author><author><name sortKey="Luo, Y" uniqKey="Luo Y">Y Luo</name></author><author><name sortKey="Jiang, Z" uniqKey="Jiang Z">Z Jiang</name></author><author><name sortKey="Ma, Y" uniqKey="Ma Y">Y Ma</name></author><author><name sortKey="Lin, Cj" uniqKey="Lin C">CJ Lin</name></author><author><name sortKey="Kim, C" uniqKey="Kim C">C Kim</name></author><author><name sortKey="Carter, Mg" uniqKey="Carter M">MG Carter</name></author><author><name sortKey="Amano, T" uniqKey="Amano T">T Amano</name></author><author><name sortKey="Park, J" uniqKey="Park J">J Park</name></author><author><name sortKey="Kish, S" uniqKey="Kish S">S Kish</name></author><author><name sortKey="Tian, Xc" uniqKey="Tian X">XC Tian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larribere, L" uniqKey="Larribere L">L Larribere</name></author><author><name sortKey="Hilmi, C" uniqKey="Hilmi C">C Hilmi</name></author><author><name sortKey="Khaled, M" uniqKey="Khaled M">M Khaled</name></author><author><name sortKey="Gaggioli, C" uniqKey="Gaggioli C">C Gaggioli</name></author><author><name sortKey="Bille, K" uniqKey="Bille K">K Bille</name></author><author><name sortKey="Auberger, P" uniqKey="Auberger P">P Auberger</name></author><author><name sortKey="Ortonne, Jp" uniqKey="Ortonne J">JP Ortonne</name></author><author><name sortKey="Ballotti, R" uniqKey="Ballotti R">R Ballotti</name></author><author><name sortKey="Bertolotto, C" uniqKey="Bertolotto C">C Bertolotto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hilmi, C" uniqKey="Hilmi C">C Hilmi</name></author><author><name sortKey="Larribere, L" uniqKey="Larribere L">L Larribere</name></author><author><name sortKey="Giuliano, S" uniqKey="Giuliano S">S Giuliano</name></author><author><name sortKey="Bille, K" uniqKey="Bille K">K Bille</name></author><author><name sortKey="Ortonne, Jp" uniqKey="Ortonne J">JP Ortonne</name></author><author><name sortKey="Ballotti, R" uniqKey="Ballotti R">R Ballotti</name></author><author><name sortKey="Bertolotto, C" uniqKey="Bertolotto C">C Bertolotto</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li></country></list><tree><country name="France"><noRegion><name sortKey="Ohanna, Mickael" sort="Ohanna, Mickael" uniqKey="Ohanna M" first="Mickaël" last="Ohanna">Mickaël Ohanna</name></noRegion><name sortKey="Allegra, Marylin" sort="Allegra, Marylin" uniqKey="Allegra M" first="Marylin" last="Allegra">Marylin Allegra</name><name sortKey="Allegra, Marylin" sort="Allegra, Marylin" uniqKey="Allegra M" first="Marylin" last="Allegra">Marylin Allegra</name><name sortKey="Bahadoran, Philippe" sort="Bahadoran, Philippe" uniqKey="Bahadoran P" first="Philippe" last="Bahadoran">Philippe Bahadoran</name><name sortKey="Bahadoran, Philippe" sort="Bahadoran, Philippe" uniqKey="Bahadoran P" first="Philippe" last="Bahadoran">Philippe Bahadoran</name><name sortKey="Bahadoran, Philippe" sort="Bahadoran, Philippe" uniqKey="Bahadoran P" first="Philippe" last="Bahadoran">Philippe Bahadoran</name><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name><name sortKey="Bertolotto, Corine" sort="Bertolotto, Corine" uniqKey="Bertolotto C" first="Corine" last="Bertolotto">Corine Bertolotto</name><name sortKey="Bertolotto, Corine" sort="Bertolotto, Corine" uniqKey="Bertolotto C" first="Corine" last="Bertolotto">Corine Bertolotto</name><name sortKey="Bille, Karine" sort="Bille, Karine" uniqKey="Bille K" first="Karine" last="Bille">Karine Bille</name><name sortKey="Bille, Karine" sort="Bille, Karine" uniqKey="Bille K" first="Karine" last="Bille">Karine Bille</name><name sortKey="Bonet, Caroline" sort="Bonet, Caroline" uniqKey="Bonet C" first="Caroline" last="Bonet">Caroline Bonet</name><name sortKey="Bonet, Caroline" sort="Bonet, Caroline" uniqKey="Bonet C" first="Caroline" last="Bonet">Caroline Bonet</name><name sortKey="Cheli, Yann" sort="Cheli, Yann" uniqKey="Cheli Y" first="Yann" last="Cheli">Yann Cheli</name><name sortKey="Cheli, Yann" sort="Cheli, Yann" uniqKey="Cheli Y" first="Yann" last="Cheli">Yann Cheli</name><name sortKey="Giacchero, Damien" sort="Giacchero, Damien" uniqKey="Giacchero D" first="Damien" last="Giacchero">Damien Giacchero</name><name sortKey="Giuliano, Sandy" sort="Giuliano, Sandy" uniqKey="Giuliano S" first="Sandy" last="Giuliano">Sandy Giuliano</name><name sortKey="Giuliano, Sandy" sort="Giuliano, Sandy" uniqKey="Giuliano S" first="Sandy" last="Giuliano">Sandy Giuliano</name><name sortKey="Lacour, Jean Philippe" sort="Lacour, Jean Philippe" uniqKey="Lacour J" first="Jean Philippe" last="Lacour">Jean Philippe Lacour</name><name sortKey="Lacour, Jean Philippe" sort="Lacour, Jean Philippe" uniqKey="Lacour J" first="Jean Philippe" last="Lacour">Jean Philippe Lacour</name><name sortKey="Ohanna, Mickael" sort="Ohanna, Mickael" uniqKey="Ohanna M" first="Mickaël" last="Ohanna">Mickaël Ohanna</name></country><country name="Australie"><noRegion><name sortKey="Bonazzi, Vanessa F" sort="Bonazzi, Vanessa F" uniqKey="Bonazzi V" first="Vanessa F" last="Bonazzi">Vanessa F. Bonazzi</name></noRegion><name sortKey="Boyle, Glen M" sort="Boyle, Glen M" uniqKey="Boyle G" first="Glen M" last="Boyle">Glen M. Boyle</name><name sortKey="Hayward, Nicholas F" sort="Hayward, Nicholas F" uniqKey="Hayward N" first="Nicholas F" last="Hayward">Nicholas F. Hayward</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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