TY - JOUR T1 - C/EBPB-dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer JF - bioRxiv DO - 10.1101/2020.08.11.244509 SP - 2020.08.11.244509 AU - Xiao-Zheng Liu AU - Anastasiia Rulina AU - Man Hung Choi AU - Line Pedersen AU - Johanna Lepland AU - Noelly Madeleine AU - Stacey D’mello Peters AU - Cara Ellen Wogsland AU - Sturla Magnus Grøndal AU - James B Lorens AU - Hani Goodarzi AU - Anders Molven AU - Per E Lønning AU - Stian Knappskog AU - Nils Halberg Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/11/2020.08.11.244509.abstract N2 - Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal (PM) breast cancer. However, the molecular mechanisms underlying this correlation are not well defined. A central phenotypic characteristic of obese individuals is increased circulating and interstitial abundance of free fatty acids. Here we demonstrate that long-term exposure to palmitic acid (PA) drives cancer cell dedifferentiation towards a cancer stem-like phenotype and enhanced tumor formation capacity. We demonstrate that this process is governed epigenetically through increased chromatin occupancy of CCAAT/enhancer-binding protein beta (C/EBPB). C/EBPB regulates cancer stem-like properties by modulating the expression of key downstream regulators of the extracellular matrix (ECM) including SERPINB2 and LCN2. Collectively, our findings demonstrate that C/EBPB plays a critical role in the initiation of cancer cells in obesity.Statement of Significance Cellular adaptation to obesity-induced palmitic acid drives tumor initiation through activation of a C/EBPB-dependent transcriptional network. This highlights a mechanistic connection between obesity and postmenopausal hormone receptor negative breast cancer.Competing Interest StatementThe authors have declared no competing interest. ER -