Vav1 as a central regulator of invadopodia assembly

Current Biology : CB
Gina L RazidloMark A McNiven

Abstract

Invadopodia are protrusive structures used by tumor cells for degradation of the extracellular matrix to promote invasion [1]. Invadopodia formation and function are regulated by cytoskeletal-remodeling pathways and the oncogenic kinase Src. The guanine nucleotide exchange factor Vav1, which is an activator of Rho family GTPases, is ectopically expressed in many pancreatic cancers, where it promotes tumor cell survival and migration [2, 3]. We have now determined that Vav1 is also a potent regulator of matrix degradation by pancreatic tumor cells as depletion of Vav1 by siRNA-mediated knockdown inhibits the formation of invadopodia. This requires the exchange function of Vav1 toward the GTPase Cdc42, which is required for invadopodia assembly [4, 5]. In addition, we have determined that Src-mediated phosphorylation and activation of Vav1 are both required for, and, unexpectedly, sufficient for, invadopodia formation. Expression of Vav1 Y174F, which mimics its activated state, is a potent inducer of invadopodia formation through Cdc42, even in the absence of Src activation and phosphorylation of other Src substrates, such as cortactin. Thus, these data identify a novel mechanism by which Vav1 can enhance the tumorigenicity and i...Continue Reading

References

Mar 1, 1997·Molecular and Cellular Biology·J HanD Broek
Mar 3, 1998·Biochemical and Biophysical Research Communications·M P LutzG Adler
Jan 15, 2000·The Journal of Biological Chemistry·M R KuhneA Weiss
Feb 12, 2000·Molecular and Cellular Biology·M López-LagoX R Bustelo
Jul 3, 2002·Nature Reviews. Immunology·Martin Turner, Daniel D Billadeau
Jan 31, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hirokazu NakaharaMikihiko Kogo
Jan 18, 2005·Cancer Cell·Martin E Fernandez-ZapicoDaniel D Billadeau
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Kent L RossmanJohn Sondek
Sep 26, 2007·Molecular and Cellular Biology·Sanita BhartiPaul A Randazzo
May 20, 2008·Nature Structural & Molecular Biology·Pilong LiMichael K Rosen
May 31, 2008·EMBO Reports·Jonathan RapleyKatrin Rittinger
Jul 15, 2009·Journal of Cell Science·Stanley S StylliPeter Lock
Aug 21, 2009·Journal of Cell Science·Renaud PoinclouxPhilippe Chavrier
Jun 24, 2011·Nature Reviews. Molecular Cell Biology·Danielle A Murphy, Sara A Courtneidge
Jul 25, 2012·European Journal of Cell Biology·Lindsy R Boateng, Anna Huttenlocher
Oct 19, 2012·Cell Adhesion & Migration·Yayu ChuangMarc Symons
Oct 26, 2012·Journal of Cell Science·Jason V EvansScott A Weed

❮ Previous
Next ❯

Citations

Nov 26, 2014·The Journal of Cell Biology·Amélie JuinFrédéric Saltel
Jul 16, 2015·The Journal of Pathology·Gordon T Brown, Graeme I Murray
Aug 13, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vladimir Mulens-AriasDomingo F Barber
Apr 11, 2014·Cell Adhesion & Migration·Lauren L LohmerDavid R Sherwood
Aug 13, 2014·European Journal of Cell Biology·Brian T Beaty, John Condeelis
Aug 9, 2016·Annual Review of Cell and Developmental Biology·Antonio Castro-CastroPhilippe Chavrier
Sep 29, 2017·Molecular Biology of the Cell·David C MorrisGonzalo M Rivera
Dec 14, 2017·The Journal of Cell Biology·Campbell D Lawson, Anne J Ridley
Feb 27, 2016·Oncotarget·Shailendra Kumar Dhar DwivediResham Bhattacharya
May 21, 2014·Cell Adhesion & Migration·Julie Di MartinoViolaine Moreau
Oct 9, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna BaruzziGiorgio Berton
Jan 26, 2021·Small GTPases·Paul RivierOlivier Destaing
Jan 23, 2021·Critical Reviews in Oncology/hematology·Yan LuoRui Kong
Apr 15, 2021·Small GTPases·Aishwarya Omble, Kiran Kulkarni
Jul 13, 2021·Cellular Signalling·Rofia BoudriaLionel Guittat

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.