Fig. 1

Role of CSCs in melanoma growth, metastasis and angiogenesis. Cytokines and growth factors transcriptionally reprogram the several transcriptional factors that mediate EMT. During EMT, cells lose the epithelial markers and acquired the mesenchymal phenotypes which help in the invasion. CSCs degrade ECM proteins through MMPs which enhance the invasion properties. Further, microenvironment associated factors trans-differentiate CSCs into endothelial-like phenotype that leads to enhance neovascularisation. Additionally, angiogenesis is enhanced through upregulation of CSCs-derived angiogenic factors such as VEGF in melanoma. The CSCs-derived exosomes contain specific miRNA that control the endothelial barriers and promote intravasation that ultimately regulates metastasis. Upon change in physiology of CSC niche, dormant metastatic CSCs reactivate and exhibit MET phenotype leading to establishment of secondary tumors. CSCs: cancer stem cells; EMT: epithelial to mesenchymal transition; MET: mesenchymal to epithelial transition; ECM: extracellular matrix; MMPs: matrix metalloproteinases; VEGF: vascular endothelial growth factor