Official PDF Translation•Acta Biochimica et Biophysica Sinica

IL15RA-STAT3-GPX4/ACSL3 signaling leads to ferroptosis resistance in pancreatic cancer

Authors: Di Wu; Zhiliang Wang; Yue Zhang; Yang Yang; Yue Yang; Guangchen Zu; Xianjun Yu; Weibo Chen; Yi Qin; Xiaowu Xu; Xuemin Chen

DOI: 10.3724/abbs.2024153Status: Verified Translated Edition

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Key Findings in This Report

• Pancreatic stellate cells (PSCs) promote ferroptosis resistance in pancreatic cancer cells through a paracrine mechanism. • IL15 secreted by PSCs activates the IL15RA-STAT3-GPX4/ACSL3 signaling axis, upregulating both GPX4 and ACSL3 to prevent lipid peroxidation. • The IL15RA-STAT3-GPX4/ACSL3 axis protects pancreatic cancer cells from ferroptosis both in vitro and in vivo, suggesting a novel therapeutic target. • Targeting this signaling pathway may overcome ferroptosis resistance and improve treatment outcomes in pancreatic ductal adenocarcinoma (PDAC).