TFEB and TFE3 are key regulators of melanoma biology

Unlike MITF-M, the melanocyte-specific isoform of MITF, TFEB, TFE3 and non-melanocyte MITF isoforms are regulated primarily by mTORC1-mediated phosphorylation at the lysosome that promotes their cytoplasmic retention. As low levels of glucose or amino acids trigger down-regulation of MITF, it is likely that on nutrient limitation some MITF functions are assumed by TFE3 and TFEB, enabling MITFLow melanoma cells to survive and proliferate. The role TFEB and TFE3 in melanoma biology and their impact on MITF-driven proliferation is poorly understood. B16/F10-luc2 mouse melanoma cells were obtained from Caliper Life Sciences (Hopkinton, MA, USA). B16F10-luc2_Mitf_sKO were generated as described in PMID: 33789714. Tfeb and Tfe3 KO were generated using guides tfe3 CGTAGAAGCTGTCAGGATCG and tfeb TGGACACGTACTGTCCACCT. KO cells were clonally isolated and validated.