RNA-Seq of 501mel and WM-266-4 melanoma cell lines transplanted into mice

Melanoma is notorious for its phenotype heterogeneity, which poses a great challenge for current therapies. Two major melanoma-phenotypes are represented by 'non-EMT-like' MITFhigh and 'EMT-like' MITFlow subpopulations, and while it is thought that transcriptional plasticity leading to a switch from one phenotype to the other drives melanoma progression, recent findings suggest that phenotype switching might not be so clear-cut in vivo. To understand the impact of MITFhigh and MITFlow cells on each other within a heterogeneous tumour we sorted the individual populations from homogeneous and heterogeneous tumours and performed RNAseq. We analysed MITFhigh and MITFlow subpopulation throughout melanoma progression and found no clear 'switch', but rather an 'adaptation' with an overlap of phenotype-defining signatures during different stages of melanoma development. Overall, when compared to homogeneous tumours, heterogeneous tumours displayed major changes in ECM-interactions with increased expression of FN1, TNC and matrix re-modellers, and alterations in the repertoire of collagens and adhesion receptors