Drivers and suppressors of triple-negative breast cancer

Authors: Wanfu Wu, Margaret Warner, Li Wang, Wei-Wei He, Ruipeng Zhao, Xiaoxiang Guan, Cindy Botero, Bo Huang, Charlotte Ion, R. Charles Coombes, Jan-Ακε Gustafsson - Proceedings of the National Academy of Sciences, PNAS 2021 cited by 45

TNBC patient-derived xenografts in mice and found that the ERβ agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERβ is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERβ functionless on genes involved in proliferation and inflammation.