FABP7 Progenitors are a Targetable Metabolic Root in theBRCA1Breast

• DOI: 10.1101/2023.11.02.565360
• Publication Date: 2023-11-05T03:25:15Z
• Authors: Curtis W. McCloskey; Bowen Zhang; Matthew Waas; Golnaz Abazari; Foram Vyas; Kazeera Aliar; Pirashaanthy Thar...; Abhijith Kuttanam...; Swami Narala; Jennifer Cruikshank; Stefan O.P. Hofer; Hartland W. Jackson; Thomas Kislinger; Hal K. Berman; Rama Khokha
• Keywords: Clonogenic assay

Abstract It has been nearly 3 decades since the discovery of BRCA1/2 genes and their link to breast cancer risk, with prophylactic mastectomy remaining primary management option for these high-risk mutation carriers. The current paucity interception strategies is due undefined, targetable precursor populations in breast. Despite known cellular alterations BRCA1 breast, epithelial at root unwarranted cell state transitions remain unresolved. Here, we identify a progenitor population that dysregulated carriers stemming from metabolic role BRCA1. This fatty-acid binding protein 7 (FABP7) expressing luminal spatially confined mammary ducts, enhanced clonogenic capacity, predicted origin mixed basal-luminal differentiation but not BRCA2 We show global H3K27 acetylation reduced within ductal FABP7 cells situ , linking non-canonical regulating acetyl-CoA pools de novo fatty acid synthesis. demonstrate capacity preferentially ablated through inhibition metabolism using an FDA-approved synthase (FASN) inhibitor. study lays foundation control dynamics mitigate risk