Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/76377
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dc.contributorDepartment of Applied Biology and Chemical Technology-
dc.creatorChen, GQ-
dc.creatorGong, RH-
dc.creatorYang, DJ-
dc.creatorZhang, G-
dc.creatorLu, AP-
dc.creatorYan, SC-
dc.creatorLin, SH-
dc.creatorBian, ZX-
dc.date.accessioned2018-05-10T02:55:52Z-
dc.date.available2018-05-10T02:55:52Z-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10397/76377-
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.rights© The Author(s) 2017en_US
dc.rightsCell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en_US
dc.rightsThe following publication Chen, G. Q., Gong, R. H., Yang, D. J., Zhang, G., Lu, A. P., Yan, S. C., ... & Bian, Z. X. (2017). Halofuginone dually regulates autophagic flux through nutrient-sensing pathways in colorectal cancer. Cell death & disease, 8(5), e2789 is available at https://doi.org/10.1038/cddis.2017.203en_US
dc.titleHalofuginone dually regulates autophagic flux through nutrient-sensing pathways in colorectal canceren_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.volume8-
dc.identifier.doi10.1038/cddis.2017.203-
dcterms.abstractAutophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition. On the other hand, HF inactivates ULK1 by downregulation of its phosphorylation sites at Ser317 and Ser777 through LKB1/AMPK signaling pathway, resulting in autophagic inhibition under nutrient-poor condition. Furthermore, Atg7-dependent autophagosome formation is also induced under nutrient-rich condition or blocked in nutrient-poor environment, respectively, upon HF treatment. More interestingly, we also found that HF inhibits glycolysis under nutrient-rich condition, whereas inhibits gluconeogenesis under nutrient-poor condition in an Atg7-dependent manner, suggesting that autophagy has a pivotal role of glucose metabolism upon HF treatment. Subsequent studies showed that HF treatment retarded tumor growth in xenograft mice fed with either standard chow diet or caloric restriction through dual regulation of autophagy in vivo. Together, HF has a dual role in autophagic modulation depending on nutritional conditions for anti-CRC.-
dcterms.accessRightsopen accessen_US
dcterms.bibliographicCitationCell death & disease, 2017, v. 8, e2789-
dcterms.isPartOfCell death & disease-
dcterms.issued2017-
dc.identifier.isiWOS:000402195700055-
dc.identifier.pmid28492544-
dc.identifier.artne2789-
dc.description.validate201805 bcrc-
dc.description.oaVersion of Recorden_US
dc.identifier.FolderNumberOA_IR/PIRAen_US
dc.description.pubStatusPublisheden_US
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