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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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Activation of the STAT3 signaling pathway by the secretome of senescent melanoma cells
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Figure 2: Activation of the STAT3 signaling pathway by the secretome of senescent melanoma cells

Mentions: Western blot with phospho-specific antibodies directed against activated ERK, AKT or STAT3 indicated that melanoma cells of different genetic backgrounds exposed to SSMC displayed a strong activation of STAT3. No consistent activation of ERK and a weak AKT phosphorylation could be observed under the same conditions (Fig. 2A).


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)

Activation of the STAT3 signaling pathway by the secretome of senescent melanoma cells
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Activation of the STAT3 signaling pathway by the secretome of senescent melanoma cells
Mentions: Western blot with phospho-specific antibodies directed against activated ERK, AKT or STAT3 indicated that melanoma cells of different genetic backgrounds exposed to SSMC displayed a strong activation of STAT3. No consistent activation of ERK and a weak AKT phosphorylation could be observed under the same conditions (Fig. 2A).

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