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CFTR modulator drugs can reduce the invasive properties of colorectal cancer cells

dc.contributor.authorVicente, Luana
dc.contributor.authorBarros, Patrícia
dc.contributor.authorGonçalves, Vânia
dc.contributor.authorOliveira, Paula
dc.contributor.authorJordan, Peter
dc.contributor.authorMatos, Paulo
dc.date.accessioned2026-03-04T16:12:45Z
dc.date.available2026-03-04T16:12:45Z
dc.date.issued2025-06-11
dc.descriptionAbstract publicado em: Mol Oncol. 2025 Jun;19 Suppl 1(Suppl 1):189. doi: 10.1002/1878-0261.70070.
dc.description.abstractIntroduction: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, driven by complex genetic, epigenetic, and microenvironmental factors. Recent findings implicate the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in CRC progression, as CFTR levels are notably reduced in sporadic CRCs, particularly in advanced and metastatic tumors, correlating with poorer patient outcomes. Additionally, cystic fibrosis (CF) patients, who carry CFTR mutations, have a 6-fold increased risk of early-onset CRC. Given recent advances in small-molecule modulators that restore CFTR function in CF patients, this study explored the potential of repositioning these modulators to address CFTR downregulation in sporadic CRC. Material and method: Using a panel of CRC cell lines, we investigated whether CFTR modulators can increase CFTR functional expression in cells with various genetic backgrounds and whether such improvements could reduce their oncogenic properties. Result and discussion: Our data show that treatment with the CFTR folding correctors VX-661 and VX-445 led to a significant, approximately three-fold increase in CFTR abundance in CRC cells expressing reduced but detectable levels of the channel. Additionally, these treatments significantly reduced the migratory and invasive behavior of Caco-2 and DLD-1 cells, particularly when combined with the CFTR potentiator VX-770. Our findings suggest that CFTR modulators may hinder the oncogenic properties of CRC cells. Further in vivo studies are necessary to fully assess their potential benefits for repositioning as a CRC treatment.eng
dc.description.sponsorshipLiga Portuguesa Contra o Cancro - Bolsa de investigação em Oncologia LPCC-NRS / Terry-Fox (TF 2023-25 PM)
dc.identifier.issn1574-7891
dc.identifier.issn1878-0261
dc.identifier.urihttp://hdl.handle.net/10400.18/11152
dc.language.isoeng
dc.peerreviewedyes
dc.relation.hasversionhttps://doi.org/10.1002/1878-0261.70070
dc.relation.ispartofMolecular Oncology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectVias de Transdução de Sinal
dc.subjectCFTR
dc.subjectCRC
dc.subjectOncogenic Properties
dc.subjectCancer-Related Mortality
dc.titleCFTR modulator drugs can reduce the invasive properties of colorectal cancer cellseng
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferenceDate2025-06
oaire.citation.conferencePlaceLisboa, Portugal
oaire.citation.titleCongress Innovative Cancer Science (EACR), 16-19 June 2025
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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