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Mutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axis

2022-11-15Journal article Restricted access
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dc.contributor.authorCarvalho, Patrícia Dias
dc.contributor.authorMartins, Flávia
dc.contributor.authorMendonça, Susana
dc.contributor.authorRibeiro, Andreia
dc.contributor.authorMachado, Ana Luísa
dc.contributor.authorCarvalho, Joana
dc.contributor.authorOliveira, Maria José
dc.contributor.authorVelho, Sérgia
dc.date.accessioned2022-12-13T18:08:25Z
dc.date.available2022-12-13T18:08:25Z
dc.date.issued2022-11-15
dc.description.abstractGenetic alterations influence the malignant potential of cancer cells, and so does thetumor microenvironment. Herein, we combined the study of KRAS oncogenic effectsin colorectal cancer cells with the influence of fibroblast-derived factors. Resultsrevealed that mutant KRAS regulates cell fate through both autonomous and nonau-tonomous signaling mechanisms. Specifically, processes such as proliferation andcell-cell aggregation were autonomously controlled by mutant KRAS independentlyof the stimulation with fibroblasts conditioned media. However, cancer cell invasionrevealed to be a KRAS-dependent nonautonomous effect, resulting from the cooper-ation between fibroblast-derived HGF and mutant KRAS regulation of C-METexpression. C-MET downregulation upon KRAS silencing rendered cells less respon-sive to HGF and thus less invasive. Yet, in one cell line, KRAS inhibition triggeredinvasion upon stimulation with fibroblasts conditioned media. Inhibition of PIK3CAoncogene did not promote invasion, thus showing a KRAS-specific effect. Moreover,the invasive capacity also depended on the HGF-C-MET axis. Overall, our studyawards oncogenic KRAS an important role in modulating the response to fibroblast-secreted factors either by promoting or impairing invasion, and depicts the HGF-C-MET axis as a putative therapeutic target to impair the invasive properties of mutantKRAS cancer cells.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDias Carvalho, P, Martins, F, Mendonça, S, et al. Mutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axis. Int J Cancer. 2022; 151( 10): 1810- 1823. doi:10.1002/ijc.34225pt_PT
dc.identifier.doihttps://doi.org/10.1002/ijc.34225pt_PT
dc.identifier.eissn1097-0215
dc.identifier.issn0020-7136
dc.identifier.urihttp://hdl.handle.net/10400.22/21188
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34225pt_PT
dc.subjectC-METpt_PT
dc.subjectColorectal cancerpt_PT
dc.subjectFibroblastspt_PT
dc.subjectInvasionpt_PT
dc.subjectKRASpt_PT
dc.titleMutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1823pt_PT
oaire.citation.startPage1810pt_PT
oaire.citation.titleInternational Journal of Cancerpt_PT
oaire.citation.volume151pt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT

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