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https://hdl.handle.net/10356/103567
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DC Field | Value | Language |
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dc.contributor.author | Lim, Maegan Miang Kee | en |
dc.contributor.author | Wee, Jonathan Wei Kiat | en |
dc.contributor.author | Soong, Jen Chi | en |
dc.contributor.author | Chua, Damien | en |
dc.contributor.author | Tan, Wei Ren | en |
dc.contributor.author | Lizwan, Marco | en |
dc.contributor.author | Li, Yinliang | en |
dc.contributor.author | Teo, Ziqiang | en |
dc.contributor.author | Goh, Wilson Wen Bin | en |
dc.contributor.author | Zhu, Pengcheng | en |
dc.contributor.author | Tan, Nguan Soon | en |
dc.date.accessioned | 2019-01-03T05:58:02Z | en |
dc.date.accessioned | 2019-12-06T21:15:34Z | - |
dc.date.available | 2019-01-03T05:58:02Z | en |
dc.date.available | 2019-12-06T21:15:34Z | - |
dc.date.issued | 2018 | en |
dc.identifier.citation | Lim, 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-z | en |
dc.identifier.uri | https://hdl.handle.net/10356/103567 | - |
dc.description.abstract | Overcoming 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 |
dc.description.sponsorship | MOE (Min. of Education, S’pore) | en |
dc.format.extent | 8 p. | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Molecular Cancer | en |
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 stated | en |
dc.subject | DRNTU::Science::Biological sciences | en |
dc.subject | Multi-drug Resistance | en |
dc.subject | Epithelial-mesenchymal Transition | en |
dc.title | Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs | en |
dc.type | Journal Article | en |
dc.contributor.school | School of Biological Sciences | en |
dc.contributor.school | Lee Kong Chian School of Medicine (LKCMedicine) | en |
dc.identifier.doi | 10.1186/s12943-018-0904-z | en |
dc.description.version | Published version | en |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
Appears in Collections: | LKCMedicine Journal Articles SBS Journal Articles |
Files in This Item:
File | Description | Size | Format | |
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Targeting metabolic flexibility via.pdf | 3.21 MB | Adobe PDF | View/Open |
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