SOX2 transactivates NRF2 to promote carboplatin resistance in lung squamous cell carcinomaOA
Lung squamous cell carcinoma(LUSC)remains a major therapeutic challenge because of its pronounced resistance to chemotherapy,particularly carboplatin.In this study,we investigate the role of SOX2,a lineage-survival oncogene,in mediating carboplatin resistance in LUSC.We demonstrate that SOX2 is highly expressed in LUSC and is significantly associated with poor prognosis.Our results show that SOX2 directly transactivates the expression of NRF2,a master regulator of cellular redox homeostasis,thereby increasing glutathione(GSH)synthesis and protecting cells from carboplatin-induced oxidative stress.Pharmacological or genetic inhibition of NRF2 effectively abrogates SOX2-mediated carboplatin resistance both in vitro and in vivo,resensitizing LUSC cells to chemotherapy.These findings highlight SOX2 as a critical redox regulator that modulates NRF2 signaling to promote carboplatin resistance in LUSC.The identification of the SOX2-NRF2 axis as a potential therapeutic target suggests that NRF2 inhibition may represent a promising strategy to overcome chemoresistance in LUSC.
Hanfei Gao;Chaomei Li;Jie Sun;Liyuan Deng;Jia Li;Zhiqiang Wu;Hu Chen
Department of Cardiothoracic Surgery,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,ChinaDepartment of Anesthesia,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,ChinaDepartment of Cardiothoracic Surgery,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,ChinaDepartment of Cardiothoracic Surgery,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,ChinaDepartment of Anesthesia,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,ChinaDepartment of Cardiothoracic Surgery,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,ChinaDepartment of Cardiothoracic Surgery,School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China Key Laboratory of Geriatic Respiratory Diseases of Sichuan Higher Education Institute,Chengdu 610500,China
医药卫生
LUSCSOX2carboplatin resistanceNRF2ROS
《Acta Biochimica et Biophysica Sinica》 2026 (3)
P.681-690,10
supported in part by the grants from the National Natural Science Foundation of China(No.81903018)the Research Foundation of the Chengdu Health Commission(Nos.2023315,2023567)the Natural Science Foundation of Sichuan(Nos.2022NSFSC1333,2023YFS0178)the CMC Excellent-talent Program(No.2024qnGzn01)the Key Clinical Specialty Construction Project of Sichuan Province(No.2024GXWKP002)and the Graduate Research and Innovation Foundation of Chengdu Medical College(No.YCX2024-01-25).
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