Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms20246215
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dc.titlePharmacological inhibition of TFF3 enhances sensitivity of CMS4 colorectal carcinoma to 5-fluorouracil through inhibition of p44/42 MAPK
dc.contributor.authorChen, R.-M.
dc.contributor.authorChiou, Y.-S.
dc.contributor.authorChong, Q.-Y.
dc.contributor.authorPoh, H.-M.
dc.contributor.authorTan, T.-Z.
dc.contributor.authorZhang, M.-Y.
dc.contributor.authorMa, L.
dc.contributor.authorZhu, T.
dc.contributor.authorPandey, V.
dc.contributor.authorSalundi, B.
dc.contributor.authorPrem Kumar, A.
dc.contributor.authorLobie, P.E.
dc.date.accessioned2021-12-09T02:56:48Z
dc.date.available2021-12-09T02:56:48Z
dc.date.issued2019
dc.identifier.citationChen, R.-M., Chiou, Y.-S., Chong, Q.-Y., Poh, H.-M., Tan, T.-Z., Zhang, M.-Y., Ma, L., Zhu, T., Pandey, V., Salundi, B., Prem Kumar, A., Lobie, P.E. (2019). Pharmacological inhibition of TFF3 enhances sensitivity of CMS4 colorectal carcinoma to 5-fluorouracil through inhibition of p44/42 MAPK. International Journal of Molecular Sciences 20 (24) : 6215. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms20246215
dc.identifier.issn1661-6596
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/209881
dc.description.abstractIncreased expression of trefoil factor 3 (TFF3) has been reported in colorectal carcinoma (CRC), being correlated with distant metastasis and poor clinical outcomes. Amongst the CRC subtypes, mesenchymal (CMS4) CRC is associated with the worst survival outcome. Herein, the functional roles of TFF3 and the pharmacological inhibition of TFF3 by a novel specific small molecule TFF3 inhibitor—2-amino-4-(4-(6-fluoro-5-methylpyridin-3-yl)phenyl)-5-oxo-4H,5Hpyrano[3,2-c]chromene-3-carbonitrile (AMPC) in CMS4 CRC was explored. Forced expression of TFF3 in CMS4 CRC cells promoted cell proliferation, cell survival, foci formation, invasion, migration, cancer stem cell like behaviour and growth in 3D Matrigel. In contrast, siRNA-mediated depletion of TFF3 or AMPC inhibition of TFF3 in CMS4 CRC cells decreased oncogenic behaviour as indicated by the above cell function assays. AMPC also inhibited tumour growth in vivo. The TFF3-stimulated oncogenic behaviour of CMS4 CRC cells was dependent on TFF3 activation of the p44/42 MAPK (ERK1/2) pathway. Furthermore, the forced expression of TFF3 decreased the sensitivity of CMS4 CRC cells to 5-fluorouracil (5-FU); while depleted TFF3 expression enhanced 5-FU sensitivity in CMS4 CRC cells. 5-FU treatment induced TFF3 expression in CMS4 CRC cells. AMPC, when used in combination with 5-FU in CMS4 CRC cells exhibited a synergistic inhibitory effect. In summary, this study provides functional evidence for TFF3 as a therapeutic target in CMS4 CRC. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2019
dc.subject5-FU
dc.subjectCancer stem cell
dc.subjectCMS4 CRC
dc.subjectERK1/2
dc.subjectTargeted therapy
dc.subjectTrefoil factor 3
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentINST OF MOLECULAR & CELL BIOLOGY
dc.description.doi10.3390/ijms20246215
dc.description.sourcetitleInternational Journal of Molecular Sciences
dc.description.volume20
dc.description.issue24
dc.description.page6215
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