TPC2 controls MITF expression and metastasis in melanoma

Recent findings by Abrahamian et al. (2024) provides new insights into the relationship between Two Pore Channel 2 (TPC2) activity and the development and progression of melanoma. Melanocyte inducing transcription factor (MITF) is a critical regulator of both melanocyte and melanoma behavior. Abrahamian et al. (2024) show that MITF-high melanoma requires BOTH Rab7a and TPC2 for proliferation, invasion and metastasis. They further identify Wnt signaling as the mediator of this phenomenon; Rab7a induces TPC2 activity in lysosomes and melanosomes, which regulates GSK-3β stability, thereby determining whether β-catenin escapes degradation and translocates to the nucleus to transcribe the MITF gene. These observations provide new insights into the relationship between ion channel function, lysosomal/melanosomal activity and control for oncogenesis and disease progression in melanoma.