SGEF Is Regulated via TWEAK/Fn14/NF-κB Signaling and Promotes Survival by Modulation of the DNA Repair Response to Temozolomide

Molecular Cancer Research : MCR
Shannon P Fortin EnsignNhan L Tran

Abstract

Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors. Despite surgical removal followed by concomitant radiation and chemotherapy with the alkylating agent temozolomide, GB tumors develop treatment resistance and ultimately recur. Impaired response to treatment occurs rapidly, conferring a median survival of just fifteen months. Thus, it is necessary to identify the genetic and signaling mechanisms that promote tumor resistance to develop targeted therapies to combat this refractory disease. Previous observations indicated that SGEF (ARHGEF26), a RhoG-specific guanine nucleotide exchange factor (GEF), is overexpressed in GB tumors and plays a role in promoting TWEAK-Fn14-mediated glioma invasion. Here, further investigation revealed an important role for SGEF in glioma cell survival. SGEF expression is upregulated by TWEAK-Fn14 signaling via NF-κB activity while shRNA-mediated reduction of SGEF expression sensitizes glioma cells to temozolomide-induced apoptosis and suppresses colony formation following temozolomide treatment. Nuclear SGEF is activated following temozolomide exposure and complexes with the DNA damage repair (DDR) protein BRCA1. Moreover, BRCA1 phosphorylation in response to ...Continue Reading

References

May 4, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y LiangM Clynes
Jul 16, 2003·Radiation Research·Gui-Rong DingJunji Miyakoshi
May 11, 2004·Molecular Biology of the Cell·Shawn M EllerbroekKeith Burridge
Aug 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pierre A RobeVincent Bours
Feb 22, 2005·Neoplasia : an International Journal for Oncology Research·Dominique B HoelzingerMichael E Berens
Oct 29, 2005·Molecular Cancer Research : MCR·Junran Zhang, Simon N Powell
Dec 21, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Markus BredelBranimir I Sikic
Feb 14, 2006·Methods in Enzymology·Rafael García-MataKeith Burridge
Nov 1, 2006·The Journal of Cell Biology·Jayesh C Patel, Jorge E Galán
Apr 5, 2007·Nature Protocols·Nicolaas A P FrankenChris van Bree
May 5, 2007·Journal of Neuro-oncology·Baisakhi RaychaudhuriMichael A Vogelbaum
May 9, 2008·International Journal of Cancer. Journal International Du Cancer·Sylvie MonferranChristine Toulas
Nov 15, 2008·The American Journal of Pathology·Bodour SalhiaJames T Rutka
Jan 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrea L RussoKevin Camphausen
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Aug 24, 2011·The Journal of Cell Biology·Raquel Domínguez-KellyRaimundo Freire
Dec 3, 2011·Nature Protocols·Christophe GuilluyRafael García-Mata
Dec 20, 2011·Trends in Molecular Medicine·Stephanie Alexander, Peter Friedl
Mar 31, 2012·Science Translational Medicine·Jennifer M MunsonRavi V Bellamkonda
May 16, 2012·FEBS Letters·Dietlind L GerloffAlvaro N A Monteiro
May 19, 2012·Expert Review of Anticancer Therapy·Tor-Christian Aase Johannessen, Rolf Bjerkvig
Jun 8, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gaspar J KitangeJann N Sarkaria
Sep 13, 2012·Molecular Cancer·Aneta KwiatkowskaMarc Symons
Oct 12, 2012·Journal of Neuro-oncology·Aditi NadkarniJann N Sarkaria

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Citations

Jun 24, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Guanglei HuYumin Xia
Feb 18, 2018·Journal of Neuro-oncology·David S HershJeffrey A Winkles
Nov 13, 2018·Cell Death Discovery·Adel Rezaei MoghadamJoseph W Gordon
May 5, 2018·Molecular Cancer Research : MCR·Alison RoosNhan L Tran

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