CEBPB-dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer
Update: 2020-08-11
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.11.244509v1?rss=1
Authors: Liu, X., Rulina, A., Choi, M. H., Pedersen, L., Lepland, J., Madeleine, N., Peters, S., Wogsland, C. E., Grondal, S. M., Lorens, J., Goodarzi, H., Molven, A., Lonning, P. E., Knappskog, S., Halberg, N.
Abstract:
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.
Copy rights belong to original authors. Visit the link for more info
http://biorxiv.org/cgi/content/short/2020.08.11.244509v1?rss=1
Authors: Liu, X., Rulina, A., Choi, M. H., Pedersen, L., Lepland, J., Madeleine, N., Peters, S., Wogsland, C. E., Grondal, S. M., Lorens, J., Goodarzi, H., Molven, A., Lonning, P. E., Knappskog, S., Halberg, N.
Abstract:
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.
Copy rights belong to original authors. Visit the link for more info
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