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.
Highlights
Melanoma cells are notoriously known for their high resistance to almost all therapeutic treatments
Both phenomena can be explained by the concept of melanoma initiating cells, which are thought to derive from the phenotypic switch of more differentiated melanoma cells [21]
We previously reported that chemotherapy drugs, used in melanoma treatment, entail a senescence-like phenotype in melanoma cells that is associated with the production of an inflammatory secretome (SSMC) endowed with protumorigenic properties [16]
Summary
Melanoma cells are notoriously known for their high resistance to almost all therapeutic treatments. It was recently proposed that the remarkable phenotypic plasticity of melanoma cells allows for the rapid development of both resistance to chemotherapeutic drugs and invasive properties [1, 2]. Within a tumor or in culture, not all the melanoma cells have the same capacity to form tumors. A small population is endowed with high tumorigenic potential and has been qualified as Melanoma Initiating Cells (MIC), even though, a reversible phenotypic switch exists between these MIC and their less tumorigenic progeny [3]. The most tumorigenic melanoma cells appear to have a poorly differentiated phenotype, with high expression of mesenchymal markers [3, 4, 7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
