RPS6KA3/RSK2-mediated phosphorylation of DRAM2 promotes lysosomal targeting and autophagic flux in melanoma.

mutant suppressed melanoma progression in vitro and in vivo by disrupting autophagy. Moreover, DRAM2 protein levels were elevated in skin cancer tissues compared to normal tissues. Collectively, our findings uncover a phosphorylation-dependent trafficking switch that bifurcates DRAM2 function between autophagy and exosome secretion, and establish the RPS6KA3/RSK2-DRAM2 axis as a critical regulator of melanoma progression. This signaling pathway may represent a promising therapeutic target for autophagy-associated malignancies.