Pathol Res Pract. 2026 May 16;284:156515. doi: 10.1016/j.prp.2026.156515. Online ahead of print.
ABSTRACT
BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women. Lipase E, hormone-sensitive type (LIPE), is a key lipase with potential regulatory roles in tumor lipid metabolism and the immune microenvironment. However, the molecular mechanisms by which LIPE regulates BC progression remain unclear.
METHODS: The Gene Expression Omnibus (GEO) database was used to download BC-related transcriptomic data. The Weishengxin platform was used for gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. TNMplot and gene expression profiling interactive analysis (GEPIA) platforms were used to obtain LIPE expression in BC tissues and at different clinical stages. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect messenger RNA (mRNA) and protein expression. Cell transfection, 5-ethynyl-2'-deoxyuridine (EdU), transwell, and wound healing assays were used to evaluate gene overexpression, cell proliferation, invasion, and migration. Commercial kits were used to measure free fatty acid (FFA) and lipoprotein lipase (LPL). Flow cytometry was used to analyze the proportion of cluster of differentiation 206 (CD206)-positive cells. In vivo experiments were conducted to validate the effects of LIPE on BC lipid metabolism and macrophage polarization. Immunohistochemistry (IHC) was used to detect CD206 and Ki-67 levels.
RESULTS: BC transcriptomic analysis identified c-x-c motif chemokine receptor 4 (CXCR4), LIPE, and cyclin-dependent kinase inhibitor 1c (CDKN1C) as potential key regulators of BC progression. GO and KEGG enrichment analyses showed that lipid droplet, acylglycerol lipase activity, regulation of lipolysis in adipocytes, and leukocyte transendothelial migration were significantly enriched. LIPE was significantly downregulated in BC-related transcriptomic datasets, BC tissues, and cells. LIPE overexpression reduced BC cell proliferation, invasion, and migration, increased FFA and LPL levels and activity, and decreased fatty acid synthase (FASN) and atp-citrate lyase (ACLY) expression. It also reduced the proportion of CD206-positive cells and the levels of interleukin-10 (IL-10) and transforming growth factor beta 1 (TGF-β1), while increasing the level of IL-1β. In vivo, LIPE overexpression decreased tumor volume and weight, and reduced FASN, ACLY, CD206, and Ki-67 levels in BC tissues.
CONCLUSION: LIPE regulates lipid metabolism and thereby influences macrophage polarization, affecting BC progression and providing new insights and targets for its mechanistic research and therapy.
PMID:42143557 | DOI:10.1016/j.prp.2026.156515