HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition

Hypoxia is a universal pathological feature of solid tumors. Hypoxic tumor cells acquire metastatic and lethal phenotypes primarily through the activities of hypoxia-inducible factor 1 alpha (HIF1α). Therefore, HIF1α is considered as a promising therapeutic target. However, HIF inhibitors have not p...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hao Geng, Hyun-Kyung Ko, Janet Pittsenbarger, Christopher T. Harvey, Changhui Xue, Qiong Liu, Sadie Wiens, Sushant K. Kachhap, Tomasz M. Beer, David Z. Qian
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ID1 hypoxia resistance HIF1 targeted-treatment Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3a9e4a94373f48bca52a168e994e4acf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3a9e4a94373f48bca52a168e994e4acf
record_format	dspace
spelling	oai:doaj.org-article:3a9e4a94373f48bca52a168e994e4acf2021-11-08T06:36:43ZHIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition2296-634X10.3389/fcell.2021.724059https://doaj.org/article/3a9e4a94373f48bca52a168e994e4acf2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.724059/fullhttps://doaj.org/toc/2296-634XHypoxia is a universal pathological feature of solid tumors. Hypoxic tumor cells acquire metastatic and lethal phenotypes primarily through the activities of hypoxia-inducible factor 1 alpha (HIF1α). Therefore, HIF1α is considered as a promising therapeutic target. However, HIF inhibitors have not proven to be effective in clinical testing. The underlying mechanism is unclear. We report that oncogenic protein ID1 is upregulated in hypoxia by HIF1α shRNA or pharmacological inhibitors. In turn, ID1 supports tumor growth in hypoxia in vitro and in xenografts in vivo, conferring adaptive survival response and resistance. Mechanistically, ID1 proteins interfere HIF1-mediated gene transcription activation, thus ID1 protein degradation is accelerated by HIF1α-dependent mechanisms in hypoxia. Inhibitions of HIF1α rescues ID1, which compensates the loss of HIF1α by the upregulation of GLS2 and glutamine metabolism, thereby switching the metabolic dependency of HIF1α -inhibited cells from glucose to glutamine.Hao GengHyun-Kyung KoJanet PittsenbargerChristopher T. HarveyChanghui XueQiong LiuSadie WiensSushant K. KachhapTomasz M. BeerDavid Z. QianFrontiers Media S.A.articleID1hypoxiaresistanceHIF1targeted-treatmentBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ID1 hypoxia resistance HIF1 targeted-treatment Biology (General) QH301-705.5
spellingShingle	ID1 hypoxia resistance HIF1 targeted-treatment Biology (General) QH301-705.5 Hao Geng Hyun-Kyung Ko Janet Pittsenbarger Christopher T. Harvey Changhui Xue Qiong Liu Sadie Wiens Sushant K. Kachhap Tomasz M. Beer David Z. Qian HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition
description	Hypoxia is a universal pathological feature of solid tumors. Hypoxic tumor cells acquire metastatic and lethal phenotypes primarily through the activities of hypoxia-inducible factor 1 alpha (HIF1α). Therefore, HIF1α is considered as a promising therapeutic target. However, HIF inhibitors have not proven to be effective in clinical testing. The underlying mechanism is unclear. We report that oncogenic protein ID1 is upregulated in hypoxia by HIF1α shRNA or pharmacological inhibitors. In turn, ID1 supports tumor growth in hypoxia in vitro and in xenografts in vivo, conferring adaptive survival response and resistance. Mechanistically, ID1 proteins interfere HIF1-mediated gene transcription activation, thus ID1 protein degradation is accelerated by HIF1α-dependent mechanisms in hypoxia. Inhibitions of HIF1α rescues ID1, which compensates the loss of HIF1α by the upregulation of GLS2 and glutamine metabolism, thereby switching the metabolic dependency of HIF1α -inhibited cells from glucose to glutamine.
format	article
author	Hao Geng Hyun-Kyung Ko Janet Pittsenbarger Christopher T. Harvey Changhui Xue Qiong Liu Sadie Wiens Sushant K. Kachhap Tomasz M. Beer David Z. Qian
author_facet	Hao Geng Hyun-Kyung Ko Janet Pittsenbarger Christopher T. Harvey Changhui Xue Qiong Liu Sadie Wiens Sushant K. Kachhap Tomasz M. Beer David Z. Qian
author_sort	Hao Geng
title	HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition
title_short	HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition
title_full	HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition
title_fullStr	HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition
title_full_unstemmed	HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition
title_sort	hif1 and id1 interplay confers adaptive survival to hif1α-inhibition
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3a9e4a94373f48bca52a168e994e4acf
work_keys_str_mv	AT haogeng hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT hyunkyungko hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT janetpittsenbarger hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT christophertharvey hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT changhuixue hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT qiongliu hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT sadiewiens hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT sushantkkachhap hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT tomaszmbeer hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition AT davidzqian hif1andid1interplayconfersadaptivesurvivaltohif1ainhibition
_version_	1718442896758145024

HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition

Ejemplares similares