CCDC50 promotes tumor growth through regulation of lysosome homeostasis

Cutaneous melanoma is characterized by lineage-specific lysosome-associated vesicular trafficking. Specifically, we report a melanoma enrichened lysophagy receptor, CCDC50, controlling lysosomal homeostasis and autolysosomal activity. We reveal that targeting CCDC50 in melanoma may be a promising therapeutic strategy, as nearly 70% of human melanomas highly express CCDC50. Moreover, targeting CCDC50 together with BRAFV600E inhibition induces synergistic function in regression of melanoma tumors, representing an alternative strategy for melanoma therapy. We performed transcriptome profiling (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT–PCR) in shCtrl and shCCDC50 cells to evaluate the melanoma growth and metastasis controlled by CCDC50. The deep sequencing results showed that CCDC50 defciency caused increased lysosome and vacuolar memebrane and blocked autophagy flux. A375 cells were transduced with lentivirus carring shCtrl or shCCDC50 plasmids. The infected cells were selected with puromycin for 7 days. The deletion of CCDC50 was confirmed by qRT-PCR and immunobloting. The shCtrl and shCCDC50 cells were collected for mRNA profilling analysis.