Ricerc@Sapienza

Melanoma is one of the most aggressive and treatment-resistant human cancers. The two-pore channel 2 (TPC2) is located on late endosomes, lysosomes and melanosomes. Here, we characterized how TPC2 knockout (KO) affected human melanoma cells derived from a metastatic site. TPC2 KO increased these cells' ability to invade the extracelullar matrix and was associated with the increased expression of mesenchymal markers ZEB-1, Vimentin and N-Cadherin, and the enhanced secretion of MMP9. TPC2 KO also activated genes regulated by YAP/TAZ, which are key regulators of tumourigenesis and metastasis.

Major signaling pathways, such as Notch, Hedgehog (Hh), Wnt/β-catenin and Hippo, are targeted by a plethora of physiological and pathological stimuli, ultimately resulting in the modulation of genes that act coordinately to establish specific biological processes. Many biological programs are strictly controlled by the assembly of multiprotein complexes into the nucleus, where a regulated recruitment of specific transcription factors and coactivators on gene promoter region leads to different transcriptional outcomes.