Journal
ONCOTARGET
Volume 4, Issue 12, Pages 2212-2224Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1143
Keywords
melanoma; senescence; secretome; STAT3
Categories
Funding
- Institut National du Cancer (INCA) [2012-112]
- Association pour la Recherche sur le Cancer [SFI20111203816]
- Canceropole PACA
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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 naive melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse.
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