The methionine cycle sustains the mesenchymal phenotype of tumor cells and drives PDA progression

In murine pancreatic ductal adenocarcinoma, liver metastases rely more on the methionine cycle than primary PDA, with mesenchymal tumor cells showing higher methionine-cycle activation.

• Why it matters: Mesenchymal traits in PDA predict poor outcomes, yet directly targeting mesenchymal tumor cells has been difficult.
• What they did: Metabolic profiling compared tumor cells from murine PDA and liver metastases, and SAHH was targeted in mesenchymal cells to lower homocysteine and glutathione.
• The result: SAHH targeting reduced antioxidant capacity and altered intracellular calcium homeostasis, leading to loss of mesenchymal markers and decreased proliferation and invasion, while high SAHH expression in mesenchymal PDA correlates with poor survival.

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