FIGURE 8.

Illustration of the potential mechanisms by which GPX4 induces platinum chemotherapeutic resistance in lung cancer brain metastasis. In brain metastatic lung cancer cells, hyperactive Wnt pathway motives the transcription factor NR2F2 binding to the promoter of target gene GPX4, promoting the transcription of GPX4. GPX4 stabilizes and posttranslationally regulates the level of GSTM1. Upregulation of both GPX4 and GSTM1 inhibits ferroptosis characterized with lipid peroxidation at the cost of high consumption of glutathione (GSH), leading to the chemotherapeutic resistance to platinum drugs