Hsp90α Promotes Chemoresistance in Pancreatic Cancer by Regulating Keap1-Nrf2 Axis and Inhibiting Ferroptosis

Overview

Journal Acta Biochim Biophys Sin (Shanghai)

Specialties Biochemistry
Biophysics

Date 2024 Aug 23

PMID 39175432

Authors

Bin Liu

Zhiyuan Chen

Zhaoxing Li

Xinya Zhao

Weigang Zhang

Ao Zhang

Longxing Wen

Xiaoming Wang

Shuying Zhou

Daohai Qian

Affiliations

Soon will be listed here.

Abstract

Chemoresistance is the primary reason for poor prognosis in patients with pancreatic cancer (PC). Recent studies have indicated that ferroptosis may improve chemoresistance, but the underlying mechanisms remain unclear. In this study, significant upregulation of heat shock protein 90α (Hsp90α) expression is detected in the peripheral blood and tissue samples of patients with chemoresistant PC. Further studies reveal that Hsp90α promotes the proliferation, migration, and invasion of a chemoresistant pancreatic cell line (Panc-1-gem) by suppressing ferroptosis. Hsp90α competitively binds to Kelch-like ECH-associated protein 1 (Keap1), liberating nuclear factor erythroid 2-related factor 2 (Nrf2) from Keap1 sequestration. Nrf2 subsequently translocates into the nucleus and activates the glutathione peroxidase 4 (GPX4) pathway, thereby suppressing ferroptosis. This process further worsens the chemoresistance of PC cells. This study provides valuable insight into potential molecular targets to overcome chemoresistance in PC. It sheds light on the intricate mechanisms linking Hsp90α and ferroptosis to chemoresistance in PC and provides a theoretical foundation for the development of novel therapeutic strategies.

Citing Articles

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Tang D, Kang R Cancer Drug Resist. 2024; 7:41.

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