Biology of the cell · 2026
ZDHHC7 Promotes Pyroptosis and Inhibits Breast Cancer Progression by Palmitoylating NLRP3.
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Tang Ke, Hu Ya, Tang Fangting, Xiao Maoliang
Аннотация
BACKGROUND: Breast cancer (BrCa) has become the most common malignant tumor among women worldwide. Inducing tumor cell pyroptosis has emerged as a potential anti-tumor strategy, although the biological effects of pyroptosis are context-dependent and may be dual-edged. The NLRP3 inflammasome is a major regulator of canonical pyroptosis. However, the role of ZDHHC7-mediated NLRP3 palmitoylation in BrCa remains unclear.
METHODS: ZDHHC7 expression was analyzed using UALCAN, Kaplan-Meier plotter, qPCR, and Western blotting. The growth and metastasis ability of cells were detected and evaluated, respectively, using the CCK-8 method and the Transwell assay. Pyroptosis was evaluated through Western blot, ELISA, and flow cytometry. NLRP3 palmitoylation was examined by acyl-biotin exchange (ABE) assay. Tumor growth was evaluated in xenograft models.
RESULTS: Compared with normal controls, ZDHHC7 is characterized by low expression in BrCa, and its low expression level is related to a decreased survival rate of patients. ZDHHC7 overexpression suppressed proliferation, migration, and invasion. Furthermore, ZDHHC7 overexpression promoted NLRP3 palmitoylation, activating the NLRP3 inflammasome, which increased levels of cleaved Caspase-1 and GSDMD-N, elevated secretion of IL-1β, IL-18, and LDH, and induced pyroptosis. These effects were partially reversed by NLRP3 inhibitor. Functional rescue experiments confirmed that NLRP3 inhibition restored the malignant phenotypes suppressed by ZDHHC7. In vivo, ZDHHC7 or NLRP3 overexpression inhibited tumor growth, reduced Ki67 expression, and increased pyroptosis markers.
CONCLUSION: ZDHHC7 may function as a tumor suppressor in BrCa by promoting NLRP3 palmitoylation, thereby activating NLRP3 inflammasome-mediated pyroptosis and inhibiting malignant progression in experimental models.
METHODS: ZDHHC7 expression was analyzed using UALCAN, Kaplan-Meier plotter, qPCR, and Western blotting. The growth and metastasis ability of cells were detected and evaluated, respectively, using the CCK-8 method and the Transwell assay. Pyroptosis was evaluated through Western blot, ELISA, and flow cytometry. NLRP3 palmitoylation was examined by acyl-biotin exchange (ABE) assay. Tumor growth was evaluated in xenograft models.
RESULTS: Compared with normal controls, ZDHHC7 is characterized by low expression in BrCa, and its low expression level is related to a decreased survival rate of patients. ZDHHC7 overexpression suppressed proliferation, migration, and invasion. Furthermore, ZDHHC7 overexpression promoted NLRP3 palmitoylation, activating the NLRP3 inflammasome, which increased levels of cleaved Caspase-1 and GSDMD-N, elevated secretion of IL-1β, IL-18, and LDH, and induced pyroptosis. These effects were partially reversed by NLRP3 inhibitor. Functional rescue experiments confirmed that NLRP3 inhibition restored the malignant phenotypes suppressed by ZDHHC7. In vivo, ZDHHC7 or NLRP3 overexpression inhibited tumor growth, reduced Ki67 expression, and increased pyroptosis markers.
CONCLUSION: ZDHHC7 may function as a tumor suppressor in BrCa by promoting NLRP3 palmitoylation, thereby activating NLRP3 inflammasome-mediated pyroptosis and inhibiting malignant progression in experimental models.