The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells
Open accessAbstract
In breast cancer, a key feature of peritumoral adipocytes is their loss of lipid content observed both in vitro and in human tumors. The free fatty acids (FFAs), released by adipocytes after lipolysis induced by tumor secretions, are transferred and stored in tumor cells as triglycerides in lipid droplets. In tumor cell lines, we demonstrate that FFAs can be released over time from lipid droplets through an adipose triglyceride lipase-dependent (ATGL-dependent) lipolytic pathway. In vivo, ATGL is expressed in human tumors where its expression correlates with tumor aggressiveness and is upregulated by contact with adipocytes. The released FFAs are then used for fatty acid β-oxidation (FAO), an active process in cancer but not normal breast epithelial cells, and regulated by coculture with adipocytes. However, in cocultivated cells, FAO is uncoupled from ATP production, leading to AMPK/acetyl-CoA carboxylase activation, a circle that maintains this state of metabolic remodeling. The increased invasive capacities of tumor cells induced by coculture are completely abrogated by inhibition of the coupled ATGL-dependent lipolysis/FAO pathways. These results show a complex metabolic symbiosis between tumor-surrounding adipocytes and cancer cells that stimulate their invasiveness, highlighting ATGL as a potential therapeutic target to impede breast cancer progression.
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PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response
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Metadata
- Authors
- Wang, Y. Y., Attané, C., Milhas, D., Dirat, B., Dauvillier, S., Guerard, A., Gilhodes, J., Lazar, I., Alet, N., Laurent, V., Le Gonidec, S., Biard, D., Hervé, C., Bost, F., Ren, G. S., Bono, F., Escourrou, G., Prentki, M., Nieto, L., Valet, P., & Muller, C.
- Venue
- JCI Insight
- Published
- 2017-02-23
- Volume
- 2
- Issue
- 4
- Pages
- e87489-e87489
- ISSN
- 2379-3708 (ISSN-L)
- OpenAlex
- W2589120174
- Cited by
- 455
- References
- 53
- FWCI
- 11.30
- Type
- journal article
- Language
- en
- Open access
- gold
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- Wang, Y. Y., Attané, C., Milhas, D., Dirat, B., Dauvillier, S., Guerard, A., Gilhodes, J., Lazar, I., Alet, N., Laurent, V., Le Gonidec, S., Biard, D., Hervé, C., Bost, F., Ren, G. S., Bono, F., Escourrou, G., Prentki, M., Nieto, L., . . . Muller, C. (2017). Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight. https://doi.org/10.1172/jci.insight.87489
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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