FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1997596656> ?p ?o ?g. }

• W1997596656 endingPage "1783" @default.
• W1997596656 startingPage "1772" @default.
• W1997596656 abstract "Recently, we proposed a new mechanism for understanding the Warburg effect in cancer metabolism. In this new paradigm, cancer-associated fibroblasts undergo aerobic glycolysis, and extrude lactate to feed adjacent cancer cells, which then drives mitochondrial biogenesis and oxidative mitochondrial metabolism in cancer cells. Thus, there is vectorial transport of energy-rich substrates from the fibroblastic tumor stroma to anabolic cancer cells. A prediction of this hypothesis is that cancer-associated fibroblasts should express MCT4, a mono-carboxylate transporter that has been implicated in lactate efflux from glycolytic muscle fibers and astrocytes in the brain. To address this issue, we co-cultured MCF7 breast cancer cells with normal fibroblasts. Interestingly, our results directly show that breast cancer cells specifically induce the expression of MCT4 in cancer-associated fibroblasts; MCF7 cells alone and fibroblasts alone, both failed to express MCT4. We also show that the expression of MCT4 in cancer-associated fibroblasts is due to oxidative stress, and can be prevented by pre-treatment with the anti-oxidant N-acetyl-cysteine. In contrast to our results with MCT4, we see that MCT1, a transporter involved in lactate uptake, is specifically upregulated in MCF7 breast cancer cells when co-cultured with fibroblasts. Virtually identical results were also obtained with primary human breast cancer samples. In human breast cancers, MCT4 selectively labels the tumor stroma, e.g., the cancer-associated fibroblast compartment. Conversely, MCT1 was selectively expressed in the epithelial cancer cells within the same tumors. Functionally, we show that overexpression of MCT4 in fibroblasts protects both MCF7 cancer cells and fibroblasts against cell death, under co-culture conditions. Thus, we provide the first evidence for the existence of a stromal-epithelial lactate shuttle in human tumors, analogous to the lactate shuttles that are essential for the normal physiological function of muscle tissue and brain. These data are consistent with the reverse Warburg effect, which states that cancer-associated fibroblasts undergo aerobic glycolysis, thereby producing lactate, which is utilized as a metabolic substrate by adjacent cancer cells. In this model, energy transfer or metabolic-coupling between the tumor stroma and epithelial cancer cells fuels tumor growth and metastasis, via oxidative mitochondrial metabolism in anabolic cancer cells. Most importantly, our current findings provide a new rationale and novel strategy for anti-cancer therapies, by employing MCT inhibitors." @default.
• W1997596656 created "2016-06-24" @default.
• W1997596656 creator A5006339979 @default.
• W1997596656 creator A5016235708 @default.
• W1997596656 creator A5016681558 @default.
• W1997596656 creator A5034535391 @default.
• W1997596656 creator A5044008862 @default.
• W1997596656 creator A5055376572 @default.
• W1997596656 creator A5055841016 @default.
• W1997596656 creator A5058219705 @default.
• W1997596656 creator A5065109915 @default.
• W1997596656 creator A5068031379 @default.
• W1997596656 creator A5074384753 @default.
• W1997596656 creator A5077605764 @default.
• W1997596656 creator A5079451346 @default.
• W1997596656 creator A5091000979 @default.
• W1997596656 date "2011-06-01" @default.
• W1997596656 modified "2023-10-13" @default.
• W1997596656 title "Evidence for a stromal-epithelial “lactate shuttle” in human tumors" @default.
• W1997596656 cites W1546709038 @default.
• W1997596656 cites W1841599385 @default.
• W1997596656 cites W1966672647 @default.
• W1997596656 cites W1969826942 @default.
• W1997596656 cites W1976143339 @default.
• W1997596656 cites W1979729004 @default.
• W1997596656 cites W1988671179 @default.
• W1997596656 cites W1990678897 @default.
• W1997596656 cites W1991222141 @default.
• W1997596656 cites W1992912831 @default.
• W1997596656 cites W2004045970 @default.
• W1997596656 cites W2004544448 @default.
• W1997596656 cites W2006171435 @default.
• W1997596656 cites W2021826830 @default.
• W1997596656 cites W2022861295 @default.
• W1997596656 cites W2026138483 @default.
• W1997596656 cites W2027488786 @default.
• W1997596656 cites W2032288068 @default.
• W1997596656 cites W2032402529 @default.
• W1997596656 cites W2033508630 @default.
• W1997596656 cites W2040744589 @default.
• W1997596656 cites W2041024692 @default.
• W1997596656 cites W2046687522 @default.
• W1997596656 cites W2046915110 @default.
• W1997596656 cites W2048458549 @default.
• W1997596656 cites W2051611091 @default.
• W1997596656 cites W2054288778 @default.
• W1997596656 cites W2055164947 @default.
• W1997596656 cites W2061468526 @default.
• W1997596656 cites W2069781304 @default.
• W1997596656 cites W2082094077 @default.
• W1997596656 cites W2086920509 @default.
• W1997596656 cites W2107028932 @default.
• W1997596656 cites W2116641094 @default.
• W1997596656 cites W2117945272 @default.
• W1997596656 cites W2122372985 @default.
• W1997596656 cites W2126497605 @default.
• W1997596656 cites W2127675410 @default.
• W1997596656 cites W2129643153 @default.
• W1997596656 cites W2133851039 @default.
• W1997596656 cites W2143647842 @default.
• W1997596656 cites W2151683534 @default.
• W1997596656 cites W2154362705 @default.
• W1997596656 cites W2154453972 @default.
• W1997596656 cites W2159494912 @default.
• W1997596656 cites W2162514162 @default.
• W1997596656 cites W2165235603 @default.
• W1997596656 cites W4247658083 @default.
• W1997596656 cites W4249079579 @default.
• W1997596656 cites W4253759977 @default.
• W1997596656 cites W68265880 @default.
• W1997596656 doi "https://doi.org/10.4161/cc.10.11.15659" @default.
• W1997596656 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3142461" @default.
• W1997596656 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21558814" @default.
• W1997596656 hasPublicationYear "2011" @default.
• W1997596656 type Work @default.
• W1997596656 sameAs 1997596656 @default.
• W1997596656 citedByCount "347" @default.
• W1997596656 countsByYear W19975966562012 @default.
• W1997596656 countsByYear W19975966562013 @default.
• W1997596656 countsByYear W19975966562014 @default.
• W1997596656 countsByYear W19975966562015 @default.
• W1997596656 countsByYear W19975966562016 @default.
• W1997596656 countsByYear W19975966562017 @default.
• W1997596656 countsByYear W19975966562018 @default.
• W1997596656 countsByYear W19975966562019 @default.
• W1997596656 countsByYear W19975966562020 @default.
• W1997596656 countsByYear W19975966562021 @default.
• W1997596656 countsByYear W19975966562022 @default.
• W1997596656 countsByYear W19975966562023 @default.
• W1997596656 crossrefType "journal-article" @default.
• W1997596656 hasAuthorship W1997596656A5006339979 @default.
• W1997596656 hasAuthorship W1997596656A5016235708 @default.
• W1997596656 hasAuthorship W1997596656A5016681558 @default.
• W1997596656 hasAuthorship W1997596656A5034535391 @default.
• W1997596656 hasAuthorship W1997596656A5044008862 @default.
• W1997596656 hasAuthorship W1997596656A5055376572 @default.
• W1997596656 hasAuthorship W1997596656A5055841016 @default.
• W1997596656 hasAuthorship W1997596656A5058219705 @default.

• next