Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation

Stylli, Stanley S.; Stacey, T. T. I; Verhagen, A. M. W.; Xu, San San; Pass, Ian; Courtneidge, Sara A.; Lock, Peter

doi:10.1242/jcs.046680

Cited by 136 publications

(188 citation statements)

References 54 publications

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“…TKS5 can form a complex with N-WASp (also known as WASL) and the upstream scaffolding proteins GRB2 and Nck in response to Src activity. In this way, TKS5 might promote actin polymerization at nascent invadopodia (Oikawa et al, 2008;Stylli et al, 2009). TKS5 is also important for the generation of reactive oxygen species (ROS) Gianni et al, 2009), which might potentiate tyrosine kinase activity at invadopodia and podosomes by inhibiting tyrosine phosphatases Weaver, 2009).…”

Section: Regulation By Phosphatidylinositolsmentioning

confidence: 99%

Signaling inputs to invadopodia and podosomes

Hoshino

Branch

Weaver

2013

Journal of Cell Science

153

175

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SummaryRemodeling of extracellular matrix (ECM) is a fundamental cell property that allows cells to alter their microenvironment and move through tissues. Invadopodia and podosomes are subcellular actin-rich structures that are specialized for matrix degradation and are formed by cancer and normal cells, respectively. Although initial studies focused on defining the core machinery of these two structures, recent studies have identified inputs from both growth factor and adhesion signaling as crucial for invasive activity. This Commentary will outline the current knowledge on the upstream signaling inputs to invadopodia and podosomes and their role in governing distinct stages of these invasive structures. We discuss invadopodia and podosomes as adhesion structures and highlight new data showing that invadopodia-associated adhesion rings promote the maturation of already-formed invadopodia. We present a model in which growth factor stimulation leads to phosphoinositide 3-kinase (PI3K) activity and formation of invadopodia, whereas adhesion signaling promotes exocytosis of proteinases at invadopodia.

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Section: Regulation By Phosphatidylinositolsmentioning

confidence: 99%

Signaling inputs to invadopodia and podosomes

Hoshino

Branch

Weaver

2013

Journal of Cell Science

153

175

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“…Src substrates participate in all of these functions and include the proteins cortactin (Bowden et al, 1999), N-WASp (Yamaguchi et al, 2005), dynamin-2 (Baldassarre et al, 2003), AMAP1 (Onodera et al, 2005), paxillin (Bowden et al, 1999), p130Cas (Brabek et al, 2004), Tsk5 (Seals et al, 2005), p190RhoGAP (Nakahara et al, 1998), AFAP110 (Gatesman et al, 2004) and caveolin . Several studies have evaluated Src activity in invadopodia formation through the ectopic expression of constitutively active Src alleles (Artym et al, 2006;Oser et al, 2009;Stylli et al, 2009). However, these activating Src mutants are rarely found in human tumors, which instead typically contain increased levels of wild-type (WT) Src expression and/or aberrant WT Src activity due to hyperactivation of upstream pathways (Yeatman, 2004).…”

Section: Introductionmentioning

confidence: 99%

Oncogenic Src requires a wild-type counterpart to regulate invadopodia maturation

Kelley

Ammer

Hayes

et al. 2010

Journal of Cell Science

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SummaryThe proto-oncogene Src tyrosine kinase (Src) is overexpressed in human cancers and is currently a target of anti-invasive therapies. Activation of Src is an essential catalyst of invadopodia production. Invadopodia are cellular structures that mediate extracellular matrix (ECM) proteolysis, allowing invasive cell types to breach confining tissue barriers. Invadopodia assembly and maturation is a multistep process, first requiring the targeting of actin-associated proteins to form pre-invadopodia, which subsequently mature by recruitment and activation of matrix metalloproteases (MMPs) that facilitate ECM degradation. We demonstrate that active, oncogenic Src alleles require the presence of a wild-type counterpart to induce ECM degradation at invadopodia sites. In addition, we identify the phosphorylation of the invadopodia regulatory protein cortactin as an important mediator of invadopodia maturation downstream of wild-type Src. Distinct phosphotyrosine-based protein-binding profiles in cells forming pre-invadopodia and mature invadopodia were identified by SH2-domain array analysis. These results indicate that although elevated Src kinase activity is required to target actin-associated proteins to pre-invadopodia, regulated Src activity is required for invadopodia maturation and matrix degradation activity. Our findings describe a previously unappreciated role for proto-oncogenic Src in enabling the invasive activity of constitutively active Src alleles.

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“…It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization. In cattle, expression of this gene has not been defined and well-studied, however, several studies were provided as it is potentially linked to the regulation of cellular actin (Bladt et al, 2003;Stylli et al, 2009), cell movement (Rivera et al, 2006), skeletal muscle differentiation/regeneration and cytoskeleton remodelling (Xu and Henkemeyer, 2009;Gehmlich et al, 2010). Among non-validated predicted genes, several predicted functional genes were identified for Limousine (n =2) and Hereford (n =20) breeds.…”

Section: Discussionmentioning

confidence: 99%

Identification of predicted genes expressed differentially in pituitary gland tissue of young growing bulls revealed by cDNA-AFLP technique

Pareek¹,

Michno²,

Smoczyński³

et al. 2013

CZECH J ANIM SCI

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Differentially expressed transcript derived fragments (TDFs) of bovine pituitary gland tissue at different developmental ages of Limousine and Hereford bulls were identified by cDNA-AFLP technique. Study revealed comparatively higher differentially expressed transcripts in 6-month Limousine bulls and 12-month Hereford bulls. The BLASTn/p analysis identified 3 and 21 predicted genes which gave significant e-values for Limousine and Hereford respectively, in assembled Bos taurus genome. The identified predicted genes expressed in bovine pituitary gland showed their mapped positions on bovine chromosomes: BTA2, 3, 5, 8, 9, 11, 12,[15][16][17][18][19][20][21][22][23] 26, and 28, respectively. Results based on TDF annotation identified 10 sequences that have BLAST hits to known annotated bovine genes and 14 sequences to unannotated contig regions in the latest gene Ensembl database Btau_4.0. Two breed specific predicted target genes were validated by qRT-PCR. Within and between breeds, qRT-PCR results revealed highly significant differences in the expression levels of bovine euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and NCK adaptor protein 2 (NCK2) predicted genes. Obtained results conclude that cDNA-AFLP is a reliable technique for studying within breed age dependent gene expression patterns.

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Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation

Cited by 136 publications

References 54 publications

Signaling inputs to invadopodia and podosomes

Signaling inputs to invadopodia and podosomes

Oncogenic Src requires a wild-type counterpart to regulate invadopodia maturation

Identification of predicted genes expressed differentially in pituitary gland tissue of young growing bulls revealed by cDNA-AFLP technique

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