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

Ohanna M, Cheli Y, Bonet C, Bonazzi VF, Allegra M, Giuliano S, Bille K, Bahadoran P, Giacchero D, Lacour JP, Boyle GM, Hayward NF, Bertolotto C, Ballotti R - Oncotarget (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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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The secretome of senescent melanoma cells enhances the melanoma initiating cell population
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Figure 1: The secretome of senescent melanoma cells enhances the melanoma initiating cell population

Mentions: We have shown that exposure of naïve melanoma cells to the SSMC increases their motility and tumorigenic properties [16]. To explore the mechanism involved in these processes, we first analyzed the effect of this secretome on the expression of mesenchymal markers. QRT-PCR experiments showed that naïve 501mel melanoma cells exposed to the secretome of melanoma cells rendered senescent by MITF silencing exhibited an increased level of SNAIL1, TWIST1, Fibronectin1, N-Cadherin (CDH2) mRNAs whereas MITF and E-Cadherin (CDH1) transcripts were markedly decreased (Fig. 1A).


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

Ohanna M, Cheli Y, Bonet C, Bonazzi VF, Allegra M, Giuliano S, Bille K, Bahadoran P, Giacchero D, Lacour JP, Boyle GM, Hayward NF, Bertolotto C, Ballotti R - Oncotarget (2013)

The secretome of senescent melanoma cells enhances the melanoma initiating cell population
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3926821&req=5

Figure 1: The secretome of senescent melanoma cells enhances the melanoma initiating cell population
Mentions: We have shown that exposure of naïve melanoma cells to the SSMC increases their motility and tumorigenic properties [16]. To explore the mechanism involved in these processes, we first analyzed the effect of this secretome on the expression of mesenchymal markers. QRT-PCR experiments showed that naïve 501mel melanoma cells exposed to the secretome of melanoma cells rendered senescent by MITF silencing exhibited an increased level of SNAIL1, TWIST1, Fibronectin1, N-Cadherin (CDH2) mRNAs whereas MITF and E-Cadherin (CDH1) transcripts were markedly decreased (Fig. 1A).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus