The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effector.

Molecular and Cellular Biology
Nicole F NeelChanning J Der

Abstract

Our recent studies implicated key and distinct roles for the highly related RalA and RalB small GTPases (82% sequence identity) in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and invasive and metastatic growth, respectively. How RalB may promote PDAC invasion and metastasis has not been determined. In light of known Ral effector functions in regulation of actin organization and secretion, we addressed a possible role for RalB in formation of invadopodia, actin-rich membrane protrusions that contribute to tissue invasion and matrix remodeling. We determined that a majority of KRAS mutant PDAC cell lines exhibited invadopodia and that expression of activated K-Ras is both necessary and sufficient for invadopodium formation. Invadopodium formation was not dependent on the canonical Raf-MEK-ERK effector pathway and was instead dependent on the Ral effector pathway. However, this process was more dependent on RalB than on RalA. Surprisingly, RalB-mediated invadopodium formation was dependent on RalBP1/RLIP76 but not Sec5 and Exo84 exocyst effector function. Unexpectedly, the requirement for RalBP1 was independent of its best known function as a GTPase-activating protein for Rho small GTPases. Instead, disruption of the ATP...Continue Reading

References

Sep 22, 1995·The Journal of Biological Chemistry·V Jullien-FloresJ H Camonis
Feb 12, 1998·The Journal of Biological Chemistry·A YamaguchiL A Feig
Dec 12, 2001·Nature Cell Biology·Serge MoskalenkoMichael A White
Feb 28, 2002·Molecular and Cellular Biology·Atsuko PolzinTimothy J Turner
Sep 21, 2002·Cancer Cell·Thijn R BrummelkampReuven Agami
Feb 19, 2003·Biochemical and Biophysical Research Communications·K M LeeM M Ouellette
Mar 7, 2003·The Journal of Biological Chemistry·Yanzhong Hu, Nahid F Mivechi
Jul 17, 2003·International Journal of Cancer. Journal International Du Cancer·Sanjay AwasthiYogesh C Awasthi
Oct 4, 2003·The Journal of Biological Chemistry·Serge MoskalenkoMichael A White
Jan 31, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hirokazu NakaharaMikihiko Kogo
Mar 17, 2004·Seminars in Cancer Biology·Paul M Campbell, Channing J Der
Apr 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Shigeru HashimotoHisataka Sabe
Jun 2, 2004·Nature Reviews. Cancer·Klaus Pantel, Ruud H Brakenhoff
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sarah E TagueCrislyn D'Souza-Schorey
Sep 16, 2004·Nature Reviews. Molecular Cell Biology·Roberto BuccioneMark A McNiven
Nov 3, 2004·Trends in Cell Biology·Gretchen A RepaskyChanning J Der
Feb 3, 2005·The Journal of Cell Biology·Hideki YamaguchiJohn Condeelis
Jun 14, 2005·Cancer Cell·Kian-Huat LimChristopher M Counter
Jun 8, 2006·Methods in Enzymology·Adam Shutes, Channing J Der
Jun 14, 2006·Cancer Metastasis Reviews·Dave S B HoonKlaus Pantel
Dec 19, 2006·Current Biology : CB·Kian-Huat LimChristopher M Counter
Aug 21, 2007·Nature Structural & Molecular Biology·Natalia MitinKent L Rossman
Jan 26, 2008·Nature Reviews. Cancer·Brian O Bodemann, Michael A White
Mar 14, 2008·Current Opinion in Cell Biology·Mario GimonaStefan Linder
Jun 11, 2008·The Journal of Cell Biology·Mika Sakurai-YagetaPhilippe Chavrier
Jun 24, 2008·Nature Reviews. Molecular Cell Biology·Antoine E Karnoub, Robert A Weinberg
Jul 5, 2008·Clinical & Experimental Metastasis·Katarina Wolf, Peter Friedl
Nov 6, 2008·Biochemical Pharmacology·Sharad S SinghalJyotsana Singhal
Jan 21, 2009·Cancer Metastasis Reviews·Roberto BuccioneInmaculada Ayala
Mar 12, 2009·Cancer Research·Vandhana Muralidharan-ChariCrislyn D'Souza-Schorey

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Citations

Jul 9, 2013·Experimental Cell Research·David F Kashatus
Jan 29, 2013·World Journal of Gastrointestinal Oncology·Ivonne RegelJörg Kleeff
Aug 13, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vladimir Mulens-AriasDomingo F Barber
Jan 24, 2014·Biochemical Society Transactions·Helen R Mott, Darerca Owen
Sep 16, 2014·Biochimica Et Biophysica Acta·Leanna R GentryChanning J Der
Jan 15, 2014·Acta Biomaterialia·Rachel J Jerrell, Aron Parekh
Oct 16, 2012·Current Biology : CB·Pascal PeschardChristopher J Marshall
Aug 13, 2014·European Journal of Cell Biology·Brian T Beaty, John Condeelis
Jan 6, 2015·Acta Pharmacologica Sinica·Sunny Guin, Dan Theodorescu
Dec 13, 2017·Cold Spring Harbor Perspectives in Medicine·Andrew M Waters, Channing J Der
Dec 3, 2017·Pharmacological Reviews·Chao Yan, Dan Theodorescu
Jun 22, 2019·Scientific Reports·Manish Kumar SinghMaria Carla Parrini
Nov 28, 2017·Small GTPases·Pauline Jeannot, Arnaud Besson
Jul 11, 2020·Cancer Metastasis Reviews·Tamás TakácsVirag Vas
Jan 23, 2021·Critical Reviews in Oncology/hematology·Yan LuoRui Kong
Dec 28, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Tammy T ChangValerie M Weaver
May 16, 2021·Developmental Biology·Jacob I MardickDavid J Reiner
Jun 3, 2021·Cancers·Jasmine CornishHelen R Mott
Sep 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Samuel G ChamberlainHelen R Mott

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