Prolonged methionine restriction induces liver cancer persistence

However, its long-term impact on cancer progression remains unknown. Here we report that prolonged methionine restriction in epithelial human liver cancer cells leads to the formation of drug-tolerant persisters.

Epithelial human HCC cells, such as HepG2 and Huh7 cells, could survive prolonged methionine restriction. The surviving cells display typical characteristics of persistent cancer cells, including slow proliferation, diminished protein synthesis, gain of mesenchymal features, and resistance to chemotherapy. RNA-seq analysis reveals that MR persisters have increased expression of genes mediating cell migration, inflammation, and stress response, yet reduced abundance of genes involved in cell cycle regulation, metabolism, detoxification, and translation.