The three-way switch operation of Rac1/RhoA GTPase-based circuit controlling amoeboid-hybrid-mesenchymal transition

Simple item page
dc.citation.firstpage6449
dc.citation.journalTitleScientific Reports
dc.citation.volumeNumber4
dc.contributor.authorHuang, Bin
dc.contributor.authorLu, Mingyang
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.authorTsarfaty, Ilan
dc.contributor.authorOnuchic, José Nelson
dc.contributor.authorBen-Jacob, Eshel
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2014-11-14T17:45:22Z
dc.date.available2014-11-14T17:45:22Z
dc.date.issued2014
dc.description.abstractMetastatic carcinoma cells exhibit at least two different phenotypes of motility and invasion - amoeboid and mesenchymal. This plasticity poses a major clinical challenge for treating metastasis, while its underlying mechanisms remain enigmatic. Transitions between these phenotypes are mediated by the Rac1/RhoA circuit that responds to external signals such as HGF/SF via c-MET pathway. Using detailed modeling of GTPase-based regulation to study the Rac1/RhoA circuit's dynamics, we found that it can operate as a three-way switch. We propose to associate the circuit's three possible states to the amoeboid, mesenchymal and amoeboid/mesenchymal hybrid phenotype. In particular, we investigated the range of existence of, and the transition between, the three states (phenotypes) in response to Grb2 and Gab1 - two downstream adaptors of c-MET. The results help to explain the regulation of metastatic cells by c-MET pathway and hence can contribute to the assessment of possible clinical interventions.
dc.identifier.citationHuang, Bin, Lu, Mingyang, Jolly, Mohit Kumar, et al.. "The three-way switch operation of Rac1/RhoA GTPase-based circuit controlling amoeboid-hybrid-mesenchymal transition." <i>Scientific Reports,</i> 4, (2014) Nature Publishing Group: 6449. http://dx.doi.org/10.1038/srep06449.
dc.identifier.doihttp://dx.doi.org/10.1038/srep06449
dc.identifier.urihttps://hdl.handle.net/1911/78271
dc.language.isoeng
dc.publisherNature Publishing Group
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.subject.keywordcomputational models
dc.subject.keywordcomputer modelling
dc.subject.keywordcancer models
dc.titleThe three-way switch operation of Rac1/RhoA GTPase-based circuit controlling amoeboid-hybrid-mesenchymal transition
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
srep06449.pdf
Size:
1.22 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications
Bioengineering Publications
BioSciences Publications
Chemistry Publications
Physics and Astronomy Publications