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Title: Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer
Authors: Loo, Ser Yue
Toh, Li Ping
Xie, William Haowei
Pathak, Elina
Tan, Wilson
Ma, Siming
Lee, May Yin
Shatishwaran, S.
Yeo, Joanna Zhen Zhen
Yuan, Ju
Ho, Yin Ying
Peh, Esther Kai Lay
Muniandy, Magendran
Torta, Federico
Chan, Jack
Tan, Tira J.
Sim, Yirong
Tan, Veronique
Tan, Benita
Madhukumar, Preetha
Yong, Wei Sean
Ong, Kong Wee
Wong, Chow Yin
Tan, Puay Hoon
Yap, Yoon Sim
Deng, Lih-Wen
Dent, Rebecca
Foo, Roger
Wenk, Markus R.
Lee, Soo Chin
Ho, Ying Swan
Lim, Elaine Hsuen
Tam, Wai Leong
Keywords: Science::Biological sciences
Issue Date: 2021
Source: Loo, S. Y., Toh, L. P., Xie, W. H., Pathak, E., Tan, W., Ma, S., Lee, M. Y., Shatishwaran, S., Yeo, J. Z. Z., Yuan, J., Ho, Y. Y., Peh, E. K. L., Muniandy, M., Torta, F., Chan, J., Tan, T. J., Sim, Y., Tan, V., Tan, B., ...Tam, W. L. (2021). Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer. Science Advances, 7(41), eabh2443-.
Project: OFIRG17may061
IAF-ICP I1901E0040
Journal: Science Advances
Abstract: Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers cancer stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial transition (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found to be potent promoters of MET that inhibit tumorigenicity in basal-like breast cancer. Cell state transitions are defined by reprogramming of lipid metabolism. Retinoids bind cognate nuclear receptors, which target lipid metabolism genes, thereby redirecting fatty acids for β-oxidation in the mesenchymal cell state towards lipid storage in the epithelial cell state. Disruptions of key metabolic enzymes mediating this flux inhibit MET. Conversely, perturbations to fatty acid oxidation (FAO) rechannel fatty acid flux and promote a more epithelial cell phenotype, blocking EMT-driven breast cancer metastasis in animal models. FAO impinges on the epigenetic control of EMT through acetyl-CoA-dependent regulation of histone acetylation on EMT genes, thus determining cell states.
ISSN: 2375-2548
DOI: 10.1126/sciadv.abh2443
Schools: School of Biological Sciences 
Organisations: Genome Institute of Singapore, A*STAR
National University of Singapore
Rights: © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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