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Metabolic interaction between cancer-associated fibroblasts (CAFs) and colorectal cancer (CRC) cells plays a major role in CRC progression. However, little is known about lipid alternations in CAFs and how these metabolic reprogramming affect CRC cells metastasis. Here, we uncover CAFs conditioned medium (CM) promote the migration of CRC cells compared with normal fibroblasts CM. CAFs undergo a lipidomic reprogramming, and accumulate more fatty acids and phospholipids. CAFs CM after protein deprivation still increase the CRC cells migration, which suggests small molecular metabolites in CAFs CM are responsible for CRC cells migration. Then, we confirm that CRC cells take up the lipids metabolites that are secreted from CAFs. Fatty acids synthase (FASN), a crucial enzyme in fatty acids synthesis, is significantly increased in CAFs. CAF-induced CRC cell migration is abolished by knockdown of FASN by siRNA or reducing the uptake of fatty acids by CRC cells by sulfo-N-succinimidyloleate sodium in vitro and CD36 monoclonal antibody in vivo. To conclude, our results provide a new insight into the mechanism of CRC metastasis and suggest FASN of CAFs or CD36 of CRC cells may be potential targets for anti-metastasis treatment in the future.
Pubmed ID: 32327627
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View all literature mentionsA multi-institutional effort to identify and quantitate, using a systems biology approach and sophisticated mass spectrometers, all of the major - and many minor - lipid species in mammalian cells, as well as to quantitate the changes in these species in response to perturbation. The goal of their research is to better understand lipid metabolism and the active role lipids play in diabetes, stroke, cancer, arthritis, Alzheimer's and other lipid-based diseases in order to facilitate development of more effective treatments. Resources available include: LIPID MAPS publications, detailed biochemical pathways, improved protocols for lipid separation and quantification, analytical tools for determining lipid quantitation, structure drawing tools for automatically drawing lipid molecular structures in stereochemical detail, and experimental data. The LIPID MAPS organization includes six lipidomics core laboratories, each specialized in extracting, identifying, and quantifying one of the major categories of mammalian lipids: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and prenol lipids. Other core laboratories and bridge projects include bioinformatics, mass spectrometric imaging, lipid synthesis, oxidized lipids, and macrophage biology and genomics.
View all literature mentionsCurated collection of human metabolite and human metabolism data which contains records for endogenous metabolites, with each metabolite entry containing detailed chemical, physical, biochemical, concentration, and disease information. This is further supplemented with thousands of NMR and MS spectra collected on purified reference metabolites.
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View all literature mentionsCell line HCT 15 is a Cancer cell line with a species of origin Homo sapiens (Human)
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