Abstract
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.
Keywords:
EGFR; GALNT14; chemotherapy resistance; glycosylation; protein stability.
MeSH terms
-
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
-
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
-
Apoptosis / drug effects
-
Apoptosis / genetics
-
Cell Line, Tumor
-
Cisplatin / pharmacology*
-
Cisplatin / therapeutic use
-
Drug Resistance, Neoplasm / drug effects
-
Drug Resistance, Neoplasm / genetics*
-
ErbB Receptors / metabolism
-
Female
-
Ferroptosis / drug effects
-
Ferroptosis / genetics
-
Gene Expression Regulation, Neoplastic
-
Glycosylation / drug effects
-
Humans
-
Middle Aged
-
N-Acetylgalactosaminyltransferases / metabolism*
-
Ovarian Neoplasms / drug therapy*
-
Ovarian Neoplasms / genetics
-
Ovarian Neoplasms / pathology
-
Ovary / pathology
-
Signal Transduction / drug effects
-
Signal Transduction / genetics
-
Sirolimus / analogs & derivatives
-
Sirolimus / pharmacology
-
Sirolimus / therapeutic use
-
TOR Serine-Threonine Kinases / antagonists & inhibitors
-
TOR Serine-Threonine Kinases / metabolism
-
Up-Regulation
Substances
-
temsirolimus
-
N-Acetylgalactosaminyltransferases
-
UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 14, human
-
MTOR protein, human
-
EGFR protein, human
-
ErbB Receptors
-
TOR Serine-Threonine Kinases
-
Cisplatin
-
Sirolimus