1271 Two-pore channel 2 affects the tumor microenvironment promoting melanoma progression

Recently, the involvement of ionic channel TPC2 in cancer has gained increasing attention, since it regulates numerous cellular functions, such as proliferation, autophagy and angiogenesis, by releasing Ca2+ response to second messenger NAADP. is also implicated all major steps tumor metastasis, namely adhesion, migration, invasion. The aim project was study role melanoma with different aggressiveness microenvironments. expression mostly localized areas human primary metastatic melanoma. Moreover, number positive cells increases proportionally Breslow Index. Similarly, using Cancer Genome Atlas, mRNA differentially expressed within melanomas, an increase that correlates a higher In vitro, inhibition Naringenin (Nar) decreases growth spheroids dose time dependent manner. decrease confirmed silencing. induces epithelial mesenchymal transition marker switch collagen invasion 3D models. Nar acts chemosensitizing agent, inhibiting spheroid growth, when used combination existing chemotherapeutic dacarbazine. Finally, treatment melanosomal but affect processing or trafficking PMEL17, decreasing melanosome secretion consequently migratory capacity cancer-associated fibroblasts. These results indicate plays active may be attractive target for drug development.