FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2990865713> ?p ?o ?g. }

• W2990865713 abstract "The mechanical microenvironment of primary breast tumors plays a substantial role in promoting tumor progression. While the transitory response of cancer cells to pathological stiffness in their native microenvironment has been well described, it is still unclear how mechanical stimuli in the primary tumor influence distant, late-stage metastatic phenotypes across time and space in absentia. Here, we show that primary tumor stiffness promotes stable, non-genetically heritable phenotypes in breast cancer cells. This mechanical memory instructs cancer cells to adopt and maintain increased cytoskeletal dynamics, traction force, and 3D invasion in vitro, in addition to promoting osteolytic bone metastasis in vivo. Furthermore, we established a mechanical conditioning (MeCo) score comprised of mechanically-regulated genes as a global gene expression measurement of tumor stiffness response. Clinically, we show that a high MeCo score is strongly associated with bone metastasis in patients. Using a discovery approach, we mechanistically traced mechanical memory in part to ERK-mediated mechanotransductive activation of RUNX2, an osteogenic gene bookmarker and bone metastasis driver. The combination of these RUNX2 traits permits the stable transactivation of osteolytic target genes that remain upregulated after cancer cells disseminate from their activating microenvironment in order to modify a distant microenvironment. Using genetic, epigenetic, and functional approaches, we were able to simulate, repress, select and extend RUNX2-mediated mechanical memory and alter cancer cell behavior accordingly. In concert with previous studies detailing the influence of biochemical properties of the primary tumor stroma on distinct metastatic phenotypes, our findings detailing the influence of biomechanical properties support a generalized model of cancer progression in which the integrated properties of the primary tumor microenvironment govern the secondary tumor microenvironment, i.e., soil instructs soil." @default.
• W2990865713 created "2019-12-05" @default.
• W2990865713 creator A5011978353 @default.
• W2990865713 creator A5012960028 @default.
• W2990865713 creator A5015274127 @default.
• W2990865713 creator A5025633248 @default.
• W2990865713 creator A5041615231 @default.
• W2990865713 creator A5044998336 @default.
• W2990865713 creator A5047608004 @default.
• W2990865713 creator A5053015905 @default.
• W2990865713 creator A5057903275 @default.
• W2990865713 creator A5067369986 @default.
• W2990865713 creator A5071524003 @default.
• W2990865713 creator A5077807984 @default.
• W2990865713 creator A5088744297 @default.
• W2990865713 date "2019-11-20" @default.
• W2990865713 modified "2023-09-28" @default.
• W2990865713 title "Breast tumor stiffness instructs bone metastasis via mechanical memory" @default.
• W2990865713 cites W1593145356 @default.
• W2990865713 cites W1798466753 @default.
• W2990865713 cites W1979594866 @default.
• W2990865713 cites W1989095124 @default.
• W2990865713 cites W1994930469 @default.
• W2990865713 cites W1999538541 @default.
• W2990865713 cites W2003404796 @default.
• W2990865713 cites W2004480757 @default.
• W2990865713 cites W2025522134 @default.
• W2990865713 cites W2040196938 @default.
• W2990865713 cites W2064045597 @default.
• W2990865713 cites W2075425296 @default.
• W2990865713 cites W2080513978 @default.
• W2990865713 cites W2085513070 @default.
• W2990865713 cites W2099052265 @default.
• W2990865713 cites W2099847814 @default.
• W2990865713 cites W2113701976 @default.
• W2990865713 cites W2114446881 @default.
• W2990865713 cites W2116910749 @default.
• W2990865713 cites W2117757143 @default.
• W2990865713 cites W2119584041 @default.
• W2990865713 cites W2126572484 @default.
• W2990865713 cites W2130687125 @default.
• W2990865713 cites W2151197248 @default.
• W2990865713 cites W2163971691 @default.
• W2990865713 cites W2191641478 @default.
• W2990865713 cites W2345356016 @default.
• W2990865713 cites W2517493150 @default.
• W2990865713 cites W2580162795 @default.
• W2990865713 cites W2608625783 @default.
• W2990865713 cites W2771222569 @default.
• W2990865713 cites W2980164311 @default.
• W2990865713 doi "https://doi.org/10.1101/847699" @default.
• W2990865713 hasPublicationYear "2019" @default.
• W2990865713 type Work @default.
• W2990865713 sameAs 2990865713 @default.
• W2990865713 citedByCount "0" @default.
• W2990865713 crossrefType "posted-content" @default.
• W2990865713 hasAuthorship W2990865713A5011978353 @default.
• W2990865713 hasAuthorship W2990865713A5012960028 @default.
• W2990865713 hasAuthorship W2990865713A5015274127 @default.
• W2990865713 hasAuthorship W2990865713A5025633248 @default.
• W2990865713 hasAuthorship W2990865713A5041615231 @default.
• W2990865713 hasAuthorship W2990865713A5044998336 @default.
• W2990865713 hasAuthorship W2990865713A5047608004 @default.
• W2990865713 hasAuthorship W2990865713A5053015905 @default.
• W2990865713 hasAuthorship W2990865713A5057903275 @default.
• W2990865713 hasAuthorship W2990865713A5067369986 @default.
• W2990865713 hasAuthorship W2990865713A5071524003 @default.
• W2990865713 hasAuthorship W2990865713A5077807984 @default.
• W2990865713 hasAuthorship W2990865713A5088744297 @default.
• W2990865713 hasBestOaLocation W29908657131 @default.
• W2990865713 hasConcept C104317684 @default.
• W2990865713 hasConcept C121608353 @default.
• W2990865713 hasConcept C127716648 @default.
• W2990865713 hasConcept C202751555 @default.
• W2990865713 hasConcept C2776107976 @default.
• W2990865713 hasConcept C2776363554 @default.
• W2990865713 hasConcept C2777783956 @default.
• W2990865713 hasConcept C2778260815 @default.
• W2990865713 hasConcept C2778287671 @default.
• W2990865713 hasConcept C2779013556 @default.
• W2990865713 hasConcept C2779256057 @default.
• W2990865713 hasConcept C2780283643 @default.
• W2990865713 hasConcept C3020616263 @default.
• W2990865713 hasConcept C41091548 @default.
• W2990865713 hasConcept C502942594 @default.
• W2990865713 hasConcept C530470458 @default.
• W2990865713 hasConcept C54355233 @default.
• W2990865713 hasConcept C86803240 @default.
• W2990865713 hasConcept C96232424 @default.
• W2990865713 hasConceptScore W2990865713C104317684 @default.
• W2990865713 hasConceptScore W2990865713C121608353 @default.
• W2990865713 hasConceptScore W2990865713C127716648 @default.
• W2990865713 hasConceptScore W2990865713C202751555 @default.
• W2990865713 hasConceptScore W2990865713C2776107976 @default.
• W2990865713 hasConceptScore W2990865713C2776363554 @default.
• W2990865713 hasConceptScore W2990865713C2777783956 @default.
• W2990865713 hasConceptScore W2990865713C2778260815 @default.
• W2990865713 hasConceptScore W2990865713C2778287671 @default.
• W2990865713 hasConceptScore W2990865713C2779013556 @default.
• W2990865713 hasConceptScore W2990865713C2779256057 @default.

• next