Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies

Cancer Cell
Young Joo JeonZe'ev Ronai

Abstract

Many tumor cells are fueled by altered metabolism and increased glutamine (Gln) dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress to breast cancer (BCa) cells promotes RNF5 association, ubiquitination, and degradation of SLC1A5/38A2. This decreases Gln uptake, levels of TCA cycle components, mTOR signaling, and proliferation while increasing autophagy and cell death. Rnf5-deficient MMTV-PyMT mammary tumors were less differentiated and showed elevated SLC1A5 expression. Whereas RNF5 depletion in MDA-MB-231 cells promoted tumorigenesis and abolished paclitaxel responsiveness, SLC1A5/38A2 knockdown elicited opposing effects. Inverse RNF5(hi)/SLC1A5/38A2(lo) expression was associated with positive prognosis in BCa. Thus, RNF5 control of Gln uptake underlies BCa response to chemotherapies.

References

Feb 3, 1995·The Journal of Biological Chemistry·E F BlommaartA J Meijer
Oct 20, 1998·Journal of Pharmaceutical and Biomedical Analysis·L R PhillipsJ G Supko
Aug 2, 2005·Nature Cell Biology·Birgit MeusserThomas Sommer
Sep 28, 2006·The Journal of Biological Chemistry·Takahiro HatanakaMitsutoshi Setou
Oct 13, 2006·Molecular and Cellular Biology·Maiko OgataKazunori Imaizumi
Mar 3, 2007·American Journal of Physiology. Cell Physiology·Bryan C FuchsBarrie P Bode
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Sep 6, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joell J GillsPhillip A Dennis
Nov 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ralph J DeBerardinisCraig B Thompson
Jul 25, 2008·Journal of the American Society of Nephrology : JASN·Kate EvansAlan Bevington
Nov 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·David R WiseCraig B Thompson
Jul 23, 2009·American Journal of Physiology. Endocrinology and Metabolism·Fiona E BairdPeter M Taylor
Aug 6, 2009·Annual Review of Genetics·Congcong He, Daniel J Klionsky
Sep 2, 2009·Microbiology and Molecular Biology Reviews : MMBR·Michele M Fluck, Brian S Schaffhausen
Dec 15, 2010·Current Opinion in Cell Biology·Gordon C ShoreScott A Oakes
Mar 3, 2011·Nature Cell Biology·Ira Tabas, David Ron
May 4, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Hiroyuki OkudairaKeiichi Kawai
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Wei LiuJames M Phang
Aug 1, 2012·Pigment Cell & Melanoma Research·Fabian V FilippDavid A Scott
Dec 6, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mohamed HassaneinPierre P Massion
May 23, 2013·Molecules and Cells·Sang Gyun KimJohn Blenis
Jun 28, 2013·Nucleic Acids Research·Wafa B'chirAlain Bruhat
Aug 31, 2013·Nature Reviews. Drug Discovery·Claudio HetzHeather P Harding
Nov 19, 2013·Molecular Cell·Riccardo BernasconiMaurizio Molinari
Jan 10, 2014·Nature Reviews. Molecular Cell Biology·Guillermo MariñoGuido Kroemer
May 9, 2014·PLoS Genetics·Marzia ScortegagnaZe'ev A Ronai
May 30, 2014·Nature Communications·Rehan AkbaniGordon B Mills

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Citations

Oct 22, 2016·Cancer Letters·Rosy FavicchioGeorgios Giamas
Feb 4, 2016·Advances in Biological Regulation·Renee C Geck, Alex Toker
Jan 3, 2016·Biochimica Et Biophysica Acta·Yangzom D Bhutia, Vadivel Ganapathy
Dec 23, 2015·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jianfei Qi, Ze'ev A Ronai
Mar 5, 2016·FEBS Letters·Elizabeth M SelwanAimee L Edinger
Aug 19, 2015·Seminars in Cell & Developmental Biology·Zhi-Yang Tsun, Richard Possemato
May 14, 2016·Nature Communications·Zhenhua XuJ Alan Diehl
Oct 27, 2015·The FEBS Journal·Elodie Villa, Jean-Ehrland Ricci
Jun 15, 2016·Annual Review of Nutrition·Julian StevensonJames A Olzmann
Aug 9, 2016·Pharmacology & Therapeutics·John P Harrelson, Michael W Lee
Aug 23, 2016·Nature Communications·Jong Ho ParkChin Ha Chung
Jan 6, 2017·Expert Opinion on Therapeutic Targets·Nicola GiulianiOvidio Bussolati
Mar 21, 2018·SLAS Discovery·Stefan Bröer
Mar 9, 2018·Molecular Biology of the Cell·Edmond Y HuangJames A Olzmann
Mar 23, 2018·The Journal of Biological Chemistry·Zhe YangRohan D Teasdale
Dec 8, 2017·Biomolecules & Therapeutics·Hye-Young Min, Ho-Young Lee
Feb 13, 2018·Oxidative Medicine and Cellular Longevity·Yoon Seon YooYoung Joo Jeon
Jun 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Matteo MorottiAdrian L Harris
Jun 19, 2019·Journal of Cellular and Molecular Medicine·Lin ChenLun-Quan Sun
Dec 25, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Humberto De VittoJames A Radosevich
Aug 21, 2019·Cold Spring Harbor Perspectives in Medicine·Katie A ThiesMichael C Ostrowski
Aug 5, 2019·Current Cancer Drug Targets·Xinjie Lu
Jul 8, 2020·Critical Reviews in Biochemistry and Molecular Biology·Xiaodan QinHui Feng
Apr 28, 2016·The Biochemical Journal·Yangzom D BhutiaVadivel Ganapathy
Sep 2, 2020·The Journal of Clinical Investigation·Ellen C de HeerAdrian L Harris
Sep 30, 2018·The Journal of Experimental Medicine·Wenyu WangQiang Yu
Mar 17, 2017·Annual Review of Biomedical Engineering·Lifeng YangDeepak Nagrath
Jan 7, 2017·BioMed Research International·Yan-Ren LinWen-Liang Chen
Mar 28, 2017·The Journal of Clinical Investigation·Arimichi OkazakiOthon Iliopoulos
Mar 23, 2018·International Journal of Molecular Sciences·Yoon Jin ChaJa Seung Koo
Apr 17, 2020·Frontiers in Oncology·Xiangyu SunYingying Xu
Jul 13, 2020·Cellular and Molecular Life Sciences : CMLS·Fang WeiZhaoyang Zeng

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