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GALNT14 通过 EGFR/mTOR 通路调控卵巢癌细胞铁死亡和凋亡。

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

机构信息

Department of Gynecology, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, The First Affiliated Hospital of Faculty of Medicine Macau University of Science & Technology, Zhuhai, Guangdong 519000, China.

Department of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510080, China.

出版信息

Future Oncol. 2022 Jan;18(2):149-161. doi: 10.2217/fon-2021-0883. Epub 2021 Oct 13.

Abstract

Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. 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. is significantly upregulated in ovarian cancer. Downregulation of significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of 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. Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.

摘要

化疗耐药性通常发生在卵巢癌中。我们旨在探讨其耐药机制。Western blot 检测 GALNT14 的表达。进一步进行细胞功能实验以研究 GALNT14 在卵巢癌中的作用。GALNT14 在卵巢癌中显著上调。下调 GALNT14 显著抑制卵巢癌细胞的凋亡和铁死亡。进一步的机制研究表明,下调 GALNT14 通过修饰 EGFR 的 O-糖基化来抑制 mTOR 通路的活性。最后,与顺铂联合使用 mTOR 抑制剂可产生促进细胞死亡的附加作用。我们的研究可能为克服卵巢癌患者对顺铂的耐药性提供一种有前途的方法。

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