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DLGAP5-induced glycolysis reprogramming reinforces macrophage M2 polarization to impact BC progression
Yanming Lin1, Jiancong Wu2, Shiru Zhang3
1Faculty of Chinese Medicine and State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macau; Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Background:
Breast cancer (BC) is ranked among the most prevalent malignant tumors in the global female population. DLGAP5 is implicated in the progression of various tumors. However, the molecular mechanisms of DLGAP5 involved in BC and TAM interactions remain unclear.
Methods:
We investigated the expression and prognostic significance of DLGAP5 in breast cancer (BC) and its association with M2 macrophage infiltration using bioinformatics and experimental methods. DLGAP5 expression was higher in BC cells (MCF-7, MDA-MB-231) than in normal breast epithelial cells (MCF-10 A), as confirmed by qRT-PCR and Western blot. Functional assays showed that DLGAP5 promoted BC cell proliferation, migration, invasion, and anti-apoptotic ability, and increased levels of PCNA, Ki67, and Bax. DLGAP5 also elevated M2 macrophage markers (Arg1, IL-10) and glycolytic enzymes (PGK1, LDHA, PKM2, HK2), and enhanced glycolysis, as indicated by ECAR and OCR measurements. Bioinformatics analysis further supported the link between DLGAP5, glycolysis, and M2 macrophage infiltration. Finally, by establishing an allograft tumor model, the regulatory effect of DLGAP5 knockdown on the malignant progression of BC was validated in vivo.
Results:
Bioinformatics analysis revealed that the upregulation of DLGAP5, which is linked to poor prognosis in breast cancer (BC), promotes glycolytic reprogramming. This metabolic shift drives macrophage M2 polarization, thereby facilitating BC progression.
Conclusion:
Our work demonstrated that DLGAP5-induced glycolysis reinforces the progression of BC by promoting the polarization of macrophages towards an M2 phenotype. The study can provide a theoretical foundation for BC treatment, pinpointing DLGAP5 as a promising biomarker.
