Single-Cell Analysis Reveals STARD10 as a Fatty Acid Metabolism Regulator of Breast Cancer Progression via the PI3K/Akt Pathway
Yining Han, Jiacheng Fan, Yue Xi, Pengxiang Zhu, Qiyue Sun, Xiaofeng LiBreast cancer is a highly heterogeneous malignancy in which fatty acid metabolism plays a critical yet insufficiently characterized role in tumor progression, immune evasion, and treatment resistance. To address this gap, we performed a comprehensive re-analysis of single-cell transcriptomic data from 62 breast cancer patients using the Non-negative Matrix Factorization (NMF) algorithm to delineate tumor cell subpopulations at single-cell resolution. Through Gene Set Enrichment Analysis (GSEA), we identified the tumor cell subgroup most significantly associated with fatty acid metabolism. Subsequent Slingshot trajectory analysis revealed STARD10 as a key regulatory gene in fatty acid metabolic reprogramming along tumor cell differentiation trajectories. In vitro functional experiments further validated that STARD10 plays a functional role in modulating fatty acid metabolism in breast cancer cells. These findings establish STARD10 as a novel molecular marker and potential therapeutic target in breast cancer, offering new insights into the metabolic mechanisms underlying tumor heterogeneity and disease progression.