Matches in SemOpenAlex for { <https://semopenalex.org/work/W2917587374> ?p ?o ?g. }
- W2917587374 endingPage "274" @default.
- W2917587374 startingPage "274" @default.
- W2917587374 abstract "Excess lactate production due to enhanced aerobic glycolysis is characteristic of malignant cancers, which is also intimately associated with poor cancer prognoses. Although tumor-associated lactate contributes to all major steps in carcinogenesis, its action mechanism remains obscure. To understand the molecular mechanism of the lactate-induced tumor metastatic process, we identified an array of lactate-responsive genes via transcriptome analysis of a metformin-induced hyper-glycolytic liver cancer model. Gene set enrichment analysis suggested E2F-RB pathway as the dominant regulator of the lactate-induced gene expression. We experimentally verified that lactate indeed activates E2F-mediated transcription by promoting E2F1 protein accumulation through a posttranscriptional mechanism. Literature-based analysis of target pathways potentially modulated by 136 top-ranked genes indicated that genes functioning in cell-cell or cell-matrix communications dominate the lactate-induced gene expression. Especially, those regulating microtubule functions, including a group of kinesin family members, were significantly up-regulated in lactate- and E2F1-dependent manners. Depletion of E2F1 or kinesins (KIF2C, KIF18B, KIF20A) led to deformation of microtubule structures, impairing cell motility as much as the deficit in lactate production. These results indicate that E2F pathway activation by tumor-associated lactate and subsequent transcriptional activation of microtubule functions play crucial roles in tumor metastasis, providing mechanistic clues to cell motility-directed anti-cancer strategies." @default.
- W2917587374 created "2019-03-02" @default.
- W2917587374 creator A5002137270 @default.
- W2917587374 creator A5007531812 @default.
- W2917587374 creator A5021593441 @default.
- W2917587374 creator A5029756043 @default.
- W2917587374 creator A5050237530 @default.
- W2917587374 creator A5066139777 @default.
- W2917587374 creator A5078915948 @default.
- W2917587374 creator A5087344527 @default.
- W2917587374 creator A5087990317 @default.
- W2917587374 creator A5089385842 @default.
- W2917587374 date "2019-02-26" @default.
- W2917587374 modified "2023-10-17" @default.
- W2917587374 title "Lactate Activates the E2F Pathway to Promote Cell Motility by Up-Regulating Microtubule Modulating Genes" @default.
- W2917587374 cites W1587423226 @default.
- W2917587374 cites W1757875555 @default.
- W2917587374 cites W1979371608 @default.
- W2917587374 cites W1979729004 @default.
- W2917587374 cites W1982369784 @default.
- W2917587374 cites W1990332595 @default.
- W2917587374 cites W1997141906 @default.
- W2917587374 cites W1999477673 @default.
- W2917587374 cites W2005900617 @default.
- W2917587374 cites W2014845629 @default.
- W2917587374 cites W2030694827 @default.
- W2917587374 cites W2041024692 @default.
- W2917587374 cites W2049918202 @default.
- W2917587374 cites W2064972175 @default.
- W2917587374 cites W2067014191 @default.
- W2917587374 cites W2073148898 @default.
- W2917587374 cites W2086920105 @default.
- W2917587374 cites W2110015442 @default.
- W2917587374 cites W2115749410 @default.
- W2917587374 cites W2117568955 @default.
- W2917587374 cites W2117692326 @default.
- W2917587374 cites W2121630405 @default.
- W2917587374 cites W2129979556 @default.
- W2917587374 cites W2130030132 @default.
- W2917587374 cites W2132566055 @default.
- W2917587374 cites W2134873805 @default.
- W2917587374 cites W2137004763 @default.
- W2917587374 cites W2140705832 @default.
- W2917587374 cites W2142370020 @default.
- W2917587374 cites W2143697743 @default.
- W2917587374 cites W2155184914 @default.
- W2917587374 cites W2279077379 @default.
- W2917587374 cites W2338481647 @default.
- W2917587374 cites W2548475758 @default.
- W2917587374 cites W2562182278 @default.
- W2917587374 cites W2743410506 @default.
- W2917587374 cites W2783334502 @default.
- W2917587374 cites W2794021196 @default.
- W2917587374 cites W2806913490 @default.
- W2917587374 cites W2886737249 @default.
- W2917587374 cites W2898785047 @default.
- W2917587374 cites W4210817206 @default.
- W2917587374 doi "https://doi.org/10.3390/cancers11030274" @default.
- W2917587374 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6468617" @default.
- W2917587374 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30813560" @default.
- W2917587374 hasPublicationYear "2019" @default.
- W2917587374 type Work @default.
- W2917587374 sameAs 2917587374 @default.
- W2917587374 citedByCount "14" @default.
- W2917587374 countsByYear W29175873742019 @default.
- W2917587374 countsByYear W29175873742020 @default.
- W2917587374 countsByYear W29175873742021 @default.
- W2917587374 countsByYear W29175873742022 @default.
- W2917587374 countsByYear W29175873742023 @default.
- W2917587374 crossrefType "journal-article" @default.
- W2917587374 hasAuthorship W2917587374A5002137270 @default.
- W2917587374 hasAuthorship W2917587374A5007531812 @default.
- W2917587374 hasAuthorship W2917587374A5021593441 @default.
- W2917587374 hasAuthorship W2917587374A5029756043 @default.
- W2917587374 hasAuthorship W2917587374A5050237530 @default.
- W2917587374 hasAuthorship W2917587374A5066139777 @default.
- W2917587374 hasAuthorship W2917587374A5078915948 @default.
- W2917587374 hasAuthorship W2917587374A5087344527 @default.
- W2917587374 hasAuthorship W2917587374A5087990317 @default.
- W2917587374 hasAuthorship W2917587374A5089385842 @default.
- W2917587374 hasBestOaLocation W29175873741 @default.
- W2917587374 hasConcept C104317684 @default.
- W2917587374 hasConcept C109156525 @default.
- W2917587374 hasConcept C121608353 @default.
- W2917587374 hasConcept C150194340 @default.
- W2917587374 hasConcept C162317418 @default.
- W2917587374 hasConcept C20418707 @default.
- W2917587374 hasConcept C502942594 @default.
- W2917587374 hasConcept C54355233 @default.
- W2917587374 hasConcept C55493867 @default.
- W2917587374 hasConcept C555283112 @default.
- W2917587374 hasConcept C58207958 @default.
- W2917587374 hasConcept C6929976 @default.
- W2917587374 hasConcept C83258922 @default.
- W2917587374 hasConcept C86339819 @default.
- W2917587374 hasConcept C86803240 @default.
- W2917587374 hasConcept C95444343 @default.
- W2917587374 hasConcept C96232424 @default.