The ubiquitin-specific protease 8 antagonizes melatonin-induced endocytic degradation of MT1 receptor to promote lung adenocarcinoma growth

•Melatonin can induce the downregulation of the MT1 receptor.•MT1 receptor internalization incurred by melatonin follows the canonical endolysosomal pathway.•The ubiquitin-specific protease 8 antagonizes the endocytic degradation of the MT1 receptor.•The suppression of ubiquitin-specific protease 8 potentiates the cancer-inhibitory effects of melatonin in vitro.•Combination of USP8 inhibition and melatonin treatment effectively deters tumor growth in xenograft mouse models.