Contribution of Snail1 in the tumour microenvironment to the regulation of melanoma progression: A target for therapeutic intervention

Resumen del póster presentado a la VIB Conferences Series: Tumor Heterogeneity, Plasticity and Therapy, celebrado virtualmente del 5 al 6 de mayo de 2021.Melanoma is a very malignant form of skin cancer due to its high metastatic abilities and resistance to therapies. MAPK pathway is hyperactivated in 90% of melanomas with mutations in BRAF responsible for approximately 50% of the cases. Tumour cells reside in a highly heterogeneous tumour microenvironment (fME), composed by local and recru ited cells including immune infiltrate cells, fibroblasts and blood vessels composed by endothelial cells and pericytes. lt has become clear that the crosstalk between tumour and stromal cells plays a key role in cancer progression. Activated fibroblasts, known as Cancer -associated fibroblasts (CAFs), are the main stromal cells within the reactive stroma and possess many pro-tumorigenic properties via secretion of growth factors, cytokines, chemokines and the degradation of extracellular matrix. 5nail1 is an epithelialto-mesenchymal transition transcription factor expressed during development and reactivated in pathological situations including cancer and fibrosis. Snail1 is expressed in activated fibroblasts associated to damaged epithelial cells in renal fibrosis and increasing evidence supports its pro-tumorigenic role when expressed in CAFs from breast or colorectal cancer. We have established BRAF-driven murine melanoma cell lines and conditional mouse models to deplete Snail1 expression in TME cells and assessed its impact on melanoma progression. Our results showthatSnail1 is highly expressed in cells from TME, predominantly in CAFs. Snail1-silencing in TME decreases tumour sizes and metastatic tumour burden in lungs. The investigation of a combination therapy cotargeting tumour cells and CAFs may provide a promising new strategy to improve patient's prognosis.Peer reviewe