GALNT14 regulates ferroptosis and apoptosis of ovarian cancer through the EGFR/mTOR pathway

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.

Automated summary

The study revealed that upregulation of GALNT14 in ovarian cancer is associated with chemoresistance. Inhibiting GALNT14 suppressed apoptosis and ferroptosis of ovarian cancer cells, and downregulating GALNT14 activity on the mTOR pathway through modifying O-glycosylation of EGFR. Finally, a synergistic effect promoting cell death was observed with a combination of an mTOR inhibitor and cisplatin.