Cdc42-interacting protein 4 is a Src substrate that regulates invadopodia and invasiveness of breast tumors by promoting MT1-MMP endocytosis

Hu, Jinghui; Mukhopadhyay, Alka; Truesdell, Peter; Chander, Harish; Mukhopadhyay, Utpal K.; Mak, Alan S.; Craig, Andrew W.B.

doi:10.1242/jcs.078014

Cited by 48 publications

(84 citation statements)

References 83 publications

(119 reference statements)

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“…Being a member of the Rho GTPases, cdc42 is known to regulate intracellular activities such as focal complex formation, integrin localization, adhesion, cell morphology, and MMP expression [27]. Knockdown of cdc42 inhibited cell motility, but increased apoptosis in NPC cells [14,28], suggesting that cdc42 is involved in progression and metastasis in NPC.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

Deng

et al. 2014

FEBS Letters

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Edited by Angel NebredaKeywords: Nasopharyngeal carcinoma Epstein-Barr virus Latent membrane protein 1 miR-204 Cdc42 Stat-3 a b s t r a c t Nasopharayngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy. It is known that microRNAs are implicated in the progression of NPC. However, the role of miR-204 in NPC is poorly understood. In this study, we found that miR-204 was down-regulated in NPC cells and tissues. Low-level expression of miR-204 was significantly associated with a more aggressive and poor prognostic phenotype of NPC. We further found that EBV-encoded latent membrane protein 1 (LMP-1) suppressed miR-204 expression by activating Stat-3. Cdc42 was identified as a direct target of miR-204. Mir-204 inhibited EBV positive C666-1 cell invasion and metastasis partly through targeting cdc42.

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Section: Discussionmentioning

confidence: 99%

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

Deng

et al. 2014

FEBS Letters

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“…Dynamin depletion impairs local matrix degradation at invadopodia (Baldassarre et al, 2003;Destaing et al, 2013;Jiang et al, 2001;McNiven et al, 2004). In addition to dynamin, the membrane-sculpting BAR (Bin-amphiphysin-Rvs) domain proteins, FBP17 (formin-binding protein 17), CIP4 (Cdc42-interacting protein 4) and ASAP1 (ArfGAP with SH3 domain, ankyrin repeat and PH domain 1), have been localized to invadopodia (Bharti et al, 2007;Hu et al, 2011;Kovacs et al, 2006;Yamamoto et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells

Bendris

Stearns

Reis

et al. 2016

Journal of Cell Science

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The ability of cancer cells to degrade the extracellular matrix and invade interstitial tissues contributes to their metastatic potential. We recently showed that overexpression of sorting nexin 9 (SNX9) leads to increased cell invasion and metastasis in animal models, which correlates with increased SNX9 protein expression in metastases from human mammary cancers. Here, we report that SNX9 expression is reduced relative to neighboring normal tissues in primary breast tumors, and progressively reduced in more aggressive stages of non-small-cell lung cancers. We show that SNX9 is localized at invadopodia where it directly binds the invadopodia marker TKS5 and negatively regulates invadopodia formation and function. SNX9 depletion increases invadopodia number and the local recruitment of MT1-MMP by decreasing its internalization. Together, these effects result in increased localized matrix degradation. We further identify SNX9 as a Src kinase substrate and show that this phosphorylation is important for SNX9 activity in regulating cell invasion, but is dispensable for its function in regulating invadopodia. The diversified changes associated with SNX9 expression in cancer highlight its importance as a central regulator of cancer cell behavior.

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“…Podosomal actin structures are formed by the WASP/N-WASP-activated Arp2/3 complex at the plasma membrane (Albiges-Rizo et al, 2009;Murphy and Courtneidge, 2011). Recently, Toca proteins have been identified as key players in podosome/invadopodia formation (Chander et al, 2012;Hu et al, 2011a;Hu et al, 2011b;Linder et al, 2000;Pichot et al, 2010;Tsuboi et al, 2009), through their self-assembling property for the activation of WASP-mediated actin polymerization. However, it is unclear how the level of Toca protein assembly is determined for proper formation and dynamic turnover of podosomes.…”

Section: Introductionmentioning

confidence: 99%

Antagonistic regulation of F-BAR protein assemblies controls actin polymerization during podosome formation

Tsujita

Kondo

Kurisu

et al. 2013

Journal of Cell Science

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Summary FBP17, an F-BAR domain protein, has emerged as a crucial factor linking the plasma membrane to WASP-mediated actin polymerization. Although it is well established that FBP17 has a powerful self-polymerizing ability that promotes actin nucleation on membranes in vitro, knowledge of inhibitory factors that counteract this activity in vivo is limited. Here, we demonstrate that the assembly of FBP17 on the plasma membranes is antagonized by PSTPIP2, another F-BAR protein implicated in auto-inflammatory disorder. Knockdown of PSTPIP2 in macrophage promotes the assembly of FBP17 as well as subsequent actin nucleation at podosomes, resulting in an enhancement of matrix degradation. This phenotype is rescued by expression of PSTPIP2 in a manner dependent on its F-BAR domain. Time-lapse total internal reflection fluorescence (TIRF) microscopy observations reveal that the self-assembly of FBP17 at the podosomal membrane initiates actin polymerization, whereas the clustering of PSTPIP2 has an opposite effect. Biochemical analysis and live-cell imaging show that PSTPIP2 inhibits actin polymerization by competing with FBP17 for assembly at artificial as well as the plasma membrane. Interestingly, the assembly of FBP17 is dependent on WASP, and its dissociation by WASP inhibition strongly induces a self-organization of PSTPIP2 at podosomes. Thus, our data uncover a previously unappreciated antagonism between different F-BAR domain assemblies that determines the threshold of actin polymerization for the formation of functional podosomes and may explain how the absence of PSTPIP2 causes auto-inflammatory disorder.

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Cdc42-interacting protein 4 is a Src substrate that regulates invadopodia and invasiveness of breast tumors by promoting MT1-MMP endocytosis

Cited by 48 publications

References 83 publications

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells

Antagonistic regulation of F-BAR protein assemblies controls actin polymerization during podosome formation

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