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Lipids are a diverse class of hydrophobic molecules that are essential for cellular homeostasis, growth and survival, and energy production. How tumors acquire lipids is under intensive investigation, as these mechanisms could provide attractive therapeutic targets for cancer. Cellular lipid metabolism is tightly regulated and responsive to environmental stimuli. Thus, lipid metabolism in cancer is heavily influenced by the tumor microenvironment. In this Review, we outline the mechanisms by which the tumor microenvironment determines the metabolic pathways used by tumors to acquire lipids. We also discuss emerging literature that reveals that lipid availability in the tumor microenvironment influences many metabolic pathways in cancers, including those not traditionally associated with lipid biology. Thus, metabolic changes instigated by the tumor microenvironment have \u2018ripple\u2019 effects throughout the densely interconnected metabolic network of cancer cells. Given the interconnectedness of tumor metabolism, we also discuss new tools and approaches to identify the lipid metabolic requirements of cancer cells in the tumor microenvironment and characterize how these requirements influence other aspects of tumor metabolism.<\/jats:p>","DOI":"10.1242\/dmm.050814","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T08:33:22Z","timestamp":1726475602000},"source":"Crossref","is-referenced-by-count":22,"title":["Metabolic ripple effects \u2013 deciphering how lipid metabolism in cancer interfaces with the tumor microenvironment"],"prefix":"10.1242","volume":"17","author":[{"given":"Patrick B.","family":"Jonker","sequence":"first","affiliation":[{"name":"University of Chicago Ben May Department for Cancer Research , , Chicago, IL 60637 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3811-3054","authenticated-orcid":false,"given":"Alexander","family":"Muir","sequence":"additional","affiliation":[{"name":"University of Chicago Ben May Department for Cancer Research , , Chicago, IL 60637 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"2024091608331333100_DMM050814C1","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1016\/j.celrep.2018.08.015","article-title":"Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation","volume":"24","author":"Ackerman","year":"2018","journal-title":"Cell Rep"},{"key":"2024091608331333100_DMM050814C2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.trecan.2019.05.004","article-title":"Cell culture medium formulation and its implications in cancer metabolism","volume":"5","author":"Ackermann","year":"2019","journal-title":"Trends Cancer Res."},{"key":"2024091608331333100_DMM050814C3","doi-asserted-by":"publisher","first-page":"159398","DOI":"10.1016\/j.bbalip.2023.159398","article-title":"Global lipid remodelling by hypoxia aggravates migratory potential in pancreatic cancer while maintaining plasma membrane homeostasis","volume":"1868","author":"Agarwala","year":"2023","journal-title":"Biochim. 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