Matches in SemOpenAlex for { <https://semopenalex.org/work/W4304013896> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W4304013896 abstract "Abstract Type 2 diabetes mellitus (T2DM) is a major risk factor for hepatocellular carcinoma (HCC). Changes in extracellular matrix (ECM) mechanics contribute to cancer development, and increased stiffness is known to promote HCC progression in cirrhotic conditions. T2DM is characterized by an accumulation of advanced glycation end products (AGEs) in the ECM; however, how this affects HCC in non-cirrhotic conditions is unclear. Here, we find that in patients and animal models AGEs promote changes in collagen architecture and enhance ECM viscoelasticity, with greater viscous dissipation and faster stress relaxation, but not changes in stiffness. High AGEs and viscoelasticity combined with oncogenic β-catenin signaling promote HCC induction, while inhibiting AGEs production, reconstituting the clearance receptor AGER1, or breaking AGE-mediated collagen crosslinks reduce viscoelasticity and HCC growth. Matrix analysis and computational modeling demonstrate that lower interconnectivity of AGEs-bundled collagen matrix, marked by shorter fiber length and greater heterogeneity, enhances viscoelasticity. Mechanistically, animal studies and 3D cell cultures show that enhanced viscoelasticity promotes HCC cell proliferation and invasion through integrin β1–Tensin 1–YAP mechanotransduction pathway. These results reveal for the first time that AGEs-mediated structural changes enhance ECM viscoelasticity, and that viscoelasticity can drive cancer progression in vivo, independent of stiffness." @default.
- W4304013896 created "2022-10-10" @default.
- W4304013896 creator A5002977194 @default.
- W4304013896 creator A5004361421 @default.
- W4304013896 creator A5015357747 @default.
- W4304013896 creator A5018047889 @default.
- W4304013896 creator A5018173206 @default.
- W4304013896 creator A5018249439 @default.
- W4304013896 creator A5026020173 @default.
- W4304013896 creator A5045288947 @default.
- W4304013896 creator A5048302674 @default.
- W4304013896 creator A5053604265 @default.
- W4304013896 creator A5053674812 @default.
- W4304013896 creator A5057135582 @default.
- W4304013896 creator A5058408384 @default.
- W4304013896 creator A5074934068 @default.
- W4304013896 creator A5075964389 @default.
- W4304013896 creator A5078881579 @default.
- W4304013896 creator A5082852521 @default.
- W4304013896 date "2022-10-10" @default.
- W4304013896 modified "2023-10-17" @default.
- W4304013896 title "Extracellular Matrix Viscoelasticity Drives Liver Cancer Progression in Pre-Cirrhotic NASH" @default.
- W4304013896 doi "https://doi.org/10.21203/rs.3.rs-2087090/v1" @default.
- W4304013896 hasPublicationYear "2022" @default.
- W4304013896 type Work @default.
- W4304013896 citedByCount "1" @default.
- W4304013896 countsByYear W43040138962023 @default.
- W4304013896 crossrefType "posted-content" @default.
- W4304013896 hasAuthorship W4304013896A5002977194 @default.
- W4304013896 hasAuthorship W4304013896A5004361421 @default.
- W4304013896 hasAuthorship W4304013896A5015357747 @default.
- W4304013896 hasAuthorship W4304013896A5018047889 @default.
- W4304013896 hasAuthorship W4304013896A5018173206 @default.
- W4304013896 hasAuthorship W4304013896A5018249439 @default.
- W4304013896 hasAuthorship W4304013896A5026020173 @default.
- W4304013896 hasAuthorship W4304013896A5045288947 @default.
- W4304013896 hasAuthorship W4304013896A5048302674 @default.
- W4304013896 hasAuthorship W4304013896A5053604265 @default.
- W4304013896 hasAuthorship W4304013896A5053674812 @default.
- W4304013896 hasAuthorship W4304013896A5057135582 @default.
- W4304013896 hasAuthorship W4304013896A5058408384 @default.
- W4304013896 hasAuthorship W4304013896A5074934068 @default.
- W4304013896 hasAuthorship W4304013896A5075964389 @default.
- W4304013896 hasAuthorship W4304013896A5078881579 @default.
- W4304013896 hasAuthorship W4304013896A5082852521 @default.
- W4304013896 hasBestOaLocation W43040138961 @default.
- W4304013896 hasConcept C121608353 @default.
- W4304013896 hasConcept C126322002 @default.
- W4304013896 hasConcept C159985019 @default.
- W4304013896 hasConcept C170493617 @default.
- W4304013896 hasConcept C181104049 @default.
- W4304013896 hasConcept C185592680 @default.
- W4304013896 hasConcept C186541917 @default.
- W4304013896 hasConcept C189165786 @default.
- W4304013896 hasConcept C192562407 @default.
- W4304013896 hasConcept C195687474 @default.
- W4304013896 hasConcept C502942594 @default.
- W4304013896 hasConcept C71924100 @default.
- W4304013896 hasConcept C86803240 @default.
- W4304013896 hasConcept C95444343 @default.
- W4304013896 hasConceptScore W4304013896C121608353 @default.
- W4304013896 hasConceptScore W4304013896C126322002 @default.
- W4304013896 hasConceptScore W4304013896C159985019 @default.
- W4304013896 hasConceptScore W4304013896C170493617 @default.
- W4304013896 hasConceptScore W4304013896C181104049 @default.
- W4304013896 hasConceptScore W4304013896C185592680 @default.
- W4304013896 hasConceptScore W4304013896C186541917 @default.
- W4304013896 hasConceptScore W4304013896C189165786 @default.
- W4304013896 hasConceptScore W4304013896C192562407 @default.
- W4304013896 hasConceptScore W4304013896C195687474 @default.
- W4304013896 hasConceptScore W4304013896C502942594 @default.
- W4304013896 hasConceptScore W4304013896C71924100 @default.
- W4304013896 hasConceptScore W4304013896C86803240 @default.
- W4304013896 hasConceptScore W4304013896C95444343 @default.
- W4304013896 hasLocation W43040138961 @default.
- W4304013896 hasOpenAccess W4304013896 @default.
- W4304013896 hasPrimaryLocation W43040138961 @default.
- W4304013896 hasRelatedWork W2010542204 @default.
- W4304013896 hasRelatedWork W2030578167 @default.
- W4304013896 hasRelatedWork W2085039514 @default.
- W4304013896 hasRelatedWork W2102488465 @default.
- W4304013896 hasRelatedWork W2140065782 @default.
- W4304013896 hasRelatedWork W2527758949 @default.
- W4304013896 hasRelatedWork W2549070824 @default.
- W4304013896 hasRelatedWork W2981896024 @default.
- W4304013896 hasRelatedWork W3018907229 @default.
- W4304013896 hasRelatedWork W4226223958 @default.
- W4304013896 isParatext "false" @default.
- W4304013896 isRetracted "false" @default.
- W4304013896 workType "article" @default.