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Endogenous Sterol Metabolites Regulate Growth of EGFR/KRAS-Dependent Tumors via LXR

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dc.contributor.author Gabitova L.
dc.contributor.author Restifo D.
dc.contributor.author Gorin A.
dc.contributor.author Manocha K.
dc.contributor.author Handorf E.
dc.contributor.author Yang D.
dc.contributor.author Cai K.
dc.contributor.author Klein-Szanto A.
dc.contributor.author Cunningham D.
dc.contributor.author Kratz L.
dc.contributor.author Herman G.
dc.contributor.author Golemis E.
dc.contributor.author Astsaturov I.
dc.date.accessioned 2018-09-18T20:36:34Z
dc.date.available 2018-09-18T20:36:34Z
dc.date.issued 2015
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/141650
dc.description.abstract © 2015 The Authors. Meiosis-activating sterols (MAS) are substrates of SC4MOL and NSDHL in the cholesterol pathway and are important for normal organismal development. Oncogenic transformation by epidermal growth factor receptor (EGFR) or RAS increases the demand for cholesterol, suggesting a possibility for metabolic interference. To test this idea in vivo, we ablated Nsdhl in adult keratinocytes expressing KRAS<sup>G12D</sup>. Strikingly, Nsdhl inactivation antagonized the growth of skin tumors while having little effect on normal skin. Loss of Nsdhl induced the expression of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, reduced the expression of low-density lipoprotein receptor (LDLR), decreased intracellular cholesterol, and was dependent on the liver X receptor (LXR) α. Importantly, EGFR signaling opposed LXRα effects on cholesterol homeostasis, whereas an EGFR inhibitor synergized with LXRα agonists in killing cancer cells. Inhibition of SC4MOL or NSDHL, or activation of LXRα by sterol metabolites, can be an effective strategy against carcinomas with activated EGFR-KRAS signaling.
dc.title Endogenous Sterol Metabolites Regulate Growth of EGFR/KRAS-Dependent Tumors via LXR
dc.type Article
dc.relation.ispartofseries-issue 11
dc.relation.ispartofseries-volume 12
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 1927
dc.source.id SCOPUS-2015-12-11-SID84942821941


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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