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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. To enable growth, proliferating cells require more molecules called fatty acids and so the levels of an enzyme involved in fatty acid production called SCD are increased.

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 SCD is activated by MITF in melanoma cells. Importantly, SCD is required for proliferation in cells with high but not low MITF levels. Since SCD inhibitors are a proposed treatment strategy, the discovery of their lack of action in cells with low MITF levels poses a major barrier to the effectiveness of SCD inhibitor-based therapy. Further, whilst inhibiting SCD in cells with high MITF does stop proliferation, this is accompanied by a switch to the metastatic state. This study therefore highlights the importance of targeting cancer cells using specific drugs depending on cell state.

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