NQO1 Triggers Neutrophil Recruitment and NET Formation to Drive Lung Metastasis of Invasive Breast Cancer.

Autor: Wang X; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California., Qu Y; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.; Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing, China., Xu Q; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.; Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing, China., Jiang Z; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.; Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing, China., Wang H; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.; Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing, China., Lin B; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China., Cao Z; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China., Pan Y; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.; Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing, China., Li S; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China., Hu Y; Experiment Center for Science and Technology, Nanjing University of Chinese Medicine, Nanjing, China., Yang H; Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China., He L; Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China., Chang H; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California., Hang B; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California., Wen H; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China., Wu H; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China., Mao JH; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California.
Jazyk: angličtina
Zdroj: Cancer research [Cancer Res] 2024 Nov 04; Vol. 84 (21), pp. 3538-3555.
DOI: 10.1158/0008-5472.CAN-24-0291
Abstrakt: Metastasis to the lungs is a leading cause of death for patients with breast cancer. Therefore, effective therapies are urgently needed to prevent and treat lung metastasis. In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness, and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in patients with breast cancer.  Significance: NQO1 stabilizes and promotes the secretion of PPIA to activate CD147 in neutrophils and stimulate NET formation, promoting breast cancer lung metastasis and providing therapeutic targets for this fatal condition.
(©2024 American Association for Cancer Research.)
Databáze: MEDLINE
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