November 14, 2019 — Colin Goding’s lab investigates how MITF regulates fatty acid metabolism in melanoma to control cell state-switching, an important contributor to cancer metastasis and therapy resistance.
In melanoma, a highly metastatic skin cancer, cells can switch between two states: proliferating but non-invasive, and non-proliferating but invasive. Since many cancer therapies target predominantly multiplying/proliferating cells, the ability of melanoma cells to switch between these states can decrease treatment effectiveness. A key regulator of the cell state-switch to proliferation in melanoma is MITF. Proliferating cells require more molecules called fatty acids so they ramp up the levels of an enzyme called SCD that is involved in fatty acid production.
Ludwig Oxford’s Yurena Vivas Garcia and colleagues from Colin Goding’s lab studied how SCD is regulated in melanoma. In their paper, published in Molecular Cell, the researchers show that MITF activates SCD in melanoma cells. Notably, SCD is required for proliferation in cells with high but not low MITF levels. Since SCD inhibitors are a proposed treatment strategy, their inefficacy in cells with low MITF levels could pose a major barrier to SCD inhibitor-based therapy. Further, while inhibiting SCD in cells with high MITF does stop their proliferation, it also pushes them into a metastatic state. This study highlights the importance of targeting cancer cells using specific drugs depending on cell state.