Lack of tumor-derived LCN2 sensitizes pancreatic cancer cells to ferroptosis induction

LCN2 regulates microbial composition, which can impact PDAC outcomes, and inhibit ferroptosis in some cancers. However, the role of tumor-derived LCN2 in mediating ferroptosis and the tumor microbiome in PDAC has not been explored.

Here, we show that human PDAC tumors with high LCN2 expression have altered expression of genes involved in ferroptosis and microbial regulation. Lacking LCN2 in PDAC cells dysregulates ferroptosis-related pathways and sensitizes cells to ferroptosis. Moreover, lacking tumor-derived LCN2 prevents tumor growth when combined with a ferroptosis inducer and was associated with changes in the tumor microbiome.