dc.contributor.authorLim, Maegan Miang Kee
dc.contributor.authorWee, Jonathan Wei Kiat
dc.contributor.authorSoong, Jen Chi
dc.contributor.authorChua, Damien
dc.contributor.authorTan, Wei Ren
dc.contributor.authorLizwan, Marco
dc.contributor.authorLi, Yinliang
dc.contributor.authorTeo, Ziqiang
dc.contributor.authorGoh, Wilson Wen Bin
dc.contributor.authorZhu, Pengcheng
dc.contributor.authorTan, Nguan Soon
dc.identifier.citationLim, M. M. K., Wee, J. W. K., Soong, J. C., Chua, D., Tan, W. R., Lizwan, M., ... Tan, N. S. (2018). Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs. Molecular Cancer, 17(1), 152-. doi:10.1186/s12943-018-0904-zen_US
dc.description.abstractOvercoming multidrug resistance has always been a major challenge in cancer treatment. Recent evidence suggested epithelial-mesenchymal transition plays a role in MDR, but the mechanism behind this link remains unclear. We found that the expression of multiple ABC transporters was elevated in concordance with an increased drug efflux in cancer cells during EMT. The metastasis-related angiopoietin-like 4 (ANGPTL4) elevates cellular ATP to transcriptionally upregulate ABC transporters expression via the Myc and NF-κB signaling pathways. ANGPTL4 deficiency reduced IC50 of anti-tumor drugs and enhanced apoptosis of cancer cells. In vivo suppression of ANGPTL4 led to higher accumulation of cisplatin-DNA adducts in primary and metastasized tumors, and a reduced metastatic tumor load. ANGPTL4 empowered cancer cells metabolic flexibility during EMT, securing ample cellular energy that fuels multiple ABC transporters to confer EMT-mediated chemoresistance. It suggests that metabolic strategies aimed at suppressing ABC transporters along with energy deprivation of EMT cancer cells may overcome drug resistance.en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent8 p.en_US
dc.relation.ispartofseriesMolecular Canceren_US
dc.rights© 2018 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stateden_US
dc.subjectEpithelial-mesenchymal Transitionen_US
dc.subjectMulti-drug Resistanceen_US
dc.subjectDRNTU::Science::Biological sciencesen_US
dc.titleTargeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugsen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.description.versionPublished versionen_US

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