Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion

Cell Death & Disease
Juan ZhangChunlai Nie

Abstract

Guanylate-binding protein 2 (GBP2) is a member of the large GTPase superfamily that is strongly induced by interferon-γ (IFN-γ). Although the biochemical characteristics of GBP2 have been reported in detail, its biological function has not been thoroughly elucidated to date. To the best of our knowledge, this study presents the first demonstration that GBP2 inhibits mitochondrial fission and cell metastasis in breast cancer cells both in vitro and in vivo. Our previous work demonstrated that dynamin-related protein 1 (Drp1)-dependent mitochondrial fission has a key role in breast cancer cell invasion. In this study, we demonstrate that GBP2 binds directly to Drp1. Elimination of Drp1 by shRNA or Mdivi-1 (a Drp1-specific inhibitor) suppressed GBP2's regulatory function. Furthermore, GBP2 blocks Drp1 translocation from the cytosol to mitochondria, thereby attenuating Drp1-dependent mitochondrial fission and breast cancer cell invasion. In summary, our data provide new insights into the function and molecular mechanisms underlying GBP2's regulation of breast cancer cell invasion.

References

Nov 30, 2000·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·D J VestalG C Sen
Aug 22, 2001·Molecular Biology of the Cell·E SmirnovaA M van der Bliek
Dec 1, 2001·The Journal of Biological Chemistry·Victoria Y GorbachevaDeborah J Vestal
Mar 26, 2004·Nature Reviews. Molecular Cell Biology·Gerrit J K Praefcke, Harvey T McMahon
May 13, 2006·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Maureen A OlszewskiDeborah J Vestal
Nov 7, 2006·Developmental Cell·David C Chan
Jun 8, 2007·The Journal of Biological Chemistry·Chuang-Rung Chang, Craig Blackstone
Aug 14, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kristina WeinländerMichael Stürzl
Jan 14, 2009·Seminars in Cancer Biology·Stéphanie GrandemangeJean-Claude Martinou
Jan 20, 2009·Journal of Molecular Biology·Nazish AbdullahApurba Kumar Sau
May 11, 2010·Molecular Medicine·Karoline LipnikChristine Hohenadl
Oct 7, 2010·Biophysical Journal·Nazish AbdullahApurba Kumar Sau
Oct 29, 2010·Nature Communications·Juan ZhangQuan Chen
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Benedikt Westermann
Dec 15, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Deborah J Vestal, Jonathan A Jeyaratnam
Mar 25, 2011·Nature·Trever G BivonaCharles L Sawyers
Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ryohei KatayamaAlice T Shaw
Apr 26, 2012·Nature Reviews. Immunology·John D MacMicking
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Aug 23, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Kyle K Payne, Masoud H Manjili
Sep 25, 2012·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Patricio GodoyJan G Hengstler
Oct 9, 2012·Carcinogenesis·Nathalie Britzen-LaurentMichael Stürzl
Oct 31, 2014·Cell Death & Disease·C NieY Wei
Feb 7, 2015·Molecular Cell·Jennifer A KashatusDavid F Kashatus
Jul 22, 2016·Signal Transduction and Targeted Therapy·Wenzhi ShenRong Xiang

❮ Previous
Next ❯

Citations

Mar 13, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dmitri I KotovMarc K Jenkins
Feb 14, 2019·The Journal of Experimental Medicine·Kyle TretinaJohn D MacMicking
Aug 30, 2018·Cell Death & Disease·Yu ZhangChunlai Nie
Apr 3, 2018·Free Radical Research·Youngjin HanYong Sang Song
Apr 11, 2019·Frontiers in Pharmacology·Petra JagustPatricia Sancho
Nov 20, 2020·Genetics and Molecular Biology·Farzaneh RahvarHossein Mozdarani
Nov 15, 2020·International Journal of Molecular Sciences·Erika L Knott, Nancy J Leidenheimer

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
co-immunoprecipitation
pull-down
Immunoprecipitation
FRET
fluorescence resonance energy transfer
Co-IP
GTPase
confocal microscopy
transfection

Software Mentioned

Proteome Discoverer
Pro Plus
Fluoview
SEQUEST
Image

Related Concepts

Related Feeds

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.