A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions

Cellular and Molecular Life Sciences : CMLS
Sally FramC M Wells

Abstract

p-21 activated 6 (PAK6), first identified as interacting with the androgen receptor (AR), is over-expressed in multiple cancer tissues and has been linked to the progression of prostate cancer, however little is known about PAK6 function in the absence of AR signaling. We report here that PAK6 is specifically required for carcinoma cell-cell dissociation downstream of hepatocyte growth factor (HGF) for both DU145 prostate cancer and HT29 colon cancer cells. Moreover, PAK6 overexpression can drive cells to escape from adhesive colonies in the absence of stimulation. We have localized PAK6 to cell-cell junctions and have detected a direct interaction between the kinase domain of PAK6 and the junctional protein IQGAP1. Co-expression of IQGAP1 and PAK6 increases cell colony escape and leads to elevated PAK6 activation. Further studies have identified a PAK6/E-cadherin/IQGAP1 complex downstream of HGF. Moreover, we find that β-catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6 substrate. We propose a unique role for PAK6, independent of AR signaling, where PAK6 drives junction disassembly during HGF-driven cell-cell dissociation via an IQGAP1/E-cadherin complex that leads to the phosphorylation of β-caten...Continue Reading

References

Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·K HerrenknechtR Kemler
Mar 1, 1994·Japanese Journal of Cancer Research : Gann·A OchiaiS Hirohashi
Sep 20, 1996·The Journal of Biological Chemistry·S KurodaK Kaibuchi
Dec 6, 1996·The Journal of Biological Chemistry·S KurodaU Kikkawa
Dec 29, 1998·The Journal of Biological Chemistry·Y D HoD B Sacks
Dec 23, 1999·The Journal of Biological Chemistry·Z LiD B Sacks
Mar 30, 2001·The Journal of Biological Chemistry·F YangZ Sun
Apr 21, 2001·Molecular and Cellular Biology·J QuA Minden
Dec 6, 2001·The Journal of Biological Chemistry·Michael W BriggsDavid B Sacks
Jan 5, 2002·Molecular Endocrinology·Suzanne R LeeSteven P Balk
Apr 12, 2002·The Journal of Biological Chemistry·Jennifer M Swart-MatarazaDavid B Sacks
Sep 24, 2002·Journal of Cell Science·Claire M WellsAnne J Ridley
May 15, 2003·Biochemical and Biophysical Research Communications·Jennifer M MatarazaDavid B Sacks
Oct 24, 2003·The Journal of Biological Chemistry·Nicolas SchrantzGary M Bokoch
Dec 4, 2003·Current Opinion in Cell Biology·Jean Paul Thiery
Nov 20, 2004·The Journal of Biological Chemistry·Ramneet KaurMichael L Lu
Aug 18, 2005·The Journal of Biological Chemistry·Jian-Guo RenDavid B Sacks
Oct 8, 2005·Cell Motility and the Cytoskeleton·C M WellsG E Jones
Mar 6, 2008·Journal of Cell Science·Encarnación LozanoVania M M Braga
Apr 22, 2008·Cellular Signalling·Tasneem AhmedClaire M Wells
Jan 27, 2009·Cancer Metastasis Reviews·Mahmut Yilmaz, Gerhard Christofori
Mar 17, 2009·Nature Cell Biology·Catherine HoganYasuyuki Fujita
Jul 25, 2009·Cellular Signalling·Michael D BrightAnne J Ridley
Aug 12, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Meng-Horng LeeStelios T Andreadis
Apr 22, 2010·Journal of Cell Science·Claire M WellsGareth E Jones
Jan 5, 2011·Frontiers in Bioscience (Landmark Edition)·Andrew WhaleClaire M Wells
Feb 26, 2011·The Journal of Biological Chemistry·Dean E McNultyRoland S Annan

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Citations

Jan 27, 2015·Trends in Cell Biology·Jessica M SmithDavid B Sacks
Nov 24, 2016·Small GTPases·Barbara E TanosEnrique Rodriguez-Boulan
May 31, 2018·Journal of Molecular Histology·Cong-Cong WuZhi-Jun Sun
Jan 20, 2019·Journal of Molecular Histology·Ping WangYipeng Liu
Feb 28, 2015·EMBO Reports·Andrew C HedmanDavid B Sacks
Apr 10, 2015·The Journal of Biological Chemistry·Byung Hak HaTitus J Boggon
Feb 25, 2017·The Biochemical Journal·Ahmad Fahim IsmailClaire M Wells
Aug 23, 2020·Biomolecules·Natini JinawathYusuke Nakamura
Apr 21, 2016·The Biochemical Journal·Bahareh TabanifarEd Manser
Oct 23, 2020·The Journal of Biological Chemistry·Andrew C HedmanDavid B Sacks
Jan 18, 2021·The Journal of Biological Chemistry·Andrew C HedmanDavid B Sacks
Apr 30, 2021·The Journal of Cell Biology·Jennifer C ErasmusVania M M Braga
Aug 28, 2021·Cancers·Tao Wei, Paul F Lambert

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Methods Mentioned

BETA
GTPases
GTPase
confocal microscopy
pulldown
pulldowns
PCR
transfection
immunoprecipitation

Software Mentioned

Andor IQ
ImageJ
ANDOR IQ Technology

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