Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion

Cortesio, Christa L.; Chan, Keefe T.; Perrin, Benjamin J.; Burton, Nick; Zhang, Sheng; Zhang, Zhong Yin; Huttenlocher, Anna

doi:10.1083/jcb.200708048

Cited by 162 publications

(164 citation statements)

References 49 publications

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“…As the invadopodia are highly dynamic actin-rich structures, we next carried out the time-lapse analysis of invadopodia formation by using SaOS-2 cells, expressing yellow fluorescent protein (YFP)-actin (Cortesio et al, 2008). The rate of invadopodia formation was determined by monitoring the accumulating rate of YFP-actin in them as previously described (Cortesio et al, 2008). As shown, the rate of invadopodia formation was significantly inhibited by suppressed expression of Ror2 (Figure 3d).…”

Section: Ror2 Has Important Functions In Ecm Degradation and Invadopomentioning

confidence: 73%

“…Invasive tumor cells form actin-rich protrusions, called invadopodia, that degrade and extend into ECMs (Bowden et al, 1999;Onodera et al, 2005;Weaver, 2006;Cortesio et al, 2008). To evaluate the ability of invadopodia formation during in vitro invasion of SaOS-2 cells, Alexa-labeled gelatin (red) was utilized as ECM (see Materials and Methods).…”

Section: Ror2 Has Important Functions In Ecm Degradation and Invadopomentioning

confidence: 99%

“…This result was further supported by the same experiment using siRNAs (control siRNA #2 and Ror2 siRNA #2) with different sequences for the identical target genes (Supplementary Figure 1c). As the invadopodia are highly dynamic actin-rich structures, we next carried out the time-lapse analysis of invadopodia formation by using SaOS-2 cells, expressing yellow fluorescent protein (YFP)-actin (Cortesio et al, 2008). The rate of invadopodia formation was determined by monitoring the accumulating rate of YFP-actin in them as previously described (Cortesio et al, 2008).…”

Section: Ror2 Has Important Functions In Ecm Degradation and Invadopomentioning

confidence: 99%

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Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling

et al. 2009

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The receptor tyrosine kinase Ror2 regulates cell migration by acting as a receptor or co-receptor for Wnt5a. Although Wnt5a has been implicated in the invasiveness of several types of tumors, the role of Ror2 in tumor invasion remains elusive. Here we show that osteosarcoma cell lines SaOS-2 and U2OS show invasive properties in vitro by activating Wnt5a/Ror2 signaling in a cell-autonomous manner. The suppressed expression of either Wnt5a or Ror2 in osteosarcoma cells inhibits cell invasiveness accompanying decreased invadopodia formation. Gene-expression profiling identified matrix metalloproteinase 13 (MMP-13) as one of the genes whose expression is downregulated in SaOS-2 cells following suppression of Ror2 expression. Reduced expression or activity of MMP-13 suppresses invasiveness of SaOS-2 cells. Moreover, expression of MMP-13 and cell invasiveness by Wnt5a/Ror2 signaling can be abrogated by an inhibitor of the Src-family protein tyrosine kinases (SFKs), suggesting the role of the SFKs in MMP-13 expression through Wnt5a/Ror2 signaling. We further show that activation of an SFK is inhibited by the suppressed expression of Ror2. Collectively, these results indicate that Wnt5a/Ror2 signaling involves the activation of a SFK, leading to MMP-13 expression, and that constitutively active Wnt5a/Ror2 signaling confers invasive properties on osteosarcoma cells in a cell-autonomous manner.

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Section: Ror2 Has Important Functions In Ecm Degradation and Invadopomentioning

confidence: 73%

Section: Ror2 Has Important Functions In Ecm Degradation and Invadopomentioning

confidence: 99%

Section: Ror2 Has Important Functions In Ecm Degradation and Invadopomentioning

confidence: 99%

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Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling

et al. 2009

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“…The transforming growth factor-␤-stimulated podosome formation seen in aortic endothelial cells requires Src (Varon et al, 2006). And Src is also required for invadopodia formation in human breast cancer cells (Artym et al, 2006;Cortesio et al, 2008). In keeping with a role for Src in podosome/invadopodia formation, many Src substrates are obligate podosome components, including cortactin, AFAP110, paxillin, p130Cas, ASAP1, and dynamin (Baldassarre et al, 2003;Brabek et al, 2004;Gatesman et al, 2004;Webb et al, 2006;Bharti et al, 2007;Clark et al, 2007;Badowski et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The Novel Adaptor Protein Tks4 (SH3PXD2B) Is Required for Functional Podosome Formation

Buschman

Bromann

Cejudo–Martín

et al. 2009

MBoC

165

283

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Metastatic cancer cells have the ability to both degrade and migrate through the extracellular matrix (ECM). Invasiveness can be correlated with the presence of dynamic actin-rich membrane structures called podosomes or invadopodia. We showed previously that the adaptor protein tyrosine kinase substrate with five Src homology 3 domains (Tks5)/Fish is required for podosome/invadopodia formation, degradation of ECM, and cancer cell invasion in vivo and in vitro. Here, we describe Tks4, a novel protein that is closely related to Tks5. This protein contains an amino-terminal Phox homology domain, four SH3 domains, and several proline-rich motifs. In Src-transformed fibroblasts, Tks4 is tyrosine phosphorylated and predominantly localized to rosettes of podosomes. We used both short hairpin RNA knockdown and mouse embryo fibroblasts lacking Tks4 to investigate its role in podosome formation. We found that lack of Tks4 resulted in incomplete podosome formation and inhibited ECM degradation. Both phenotypes were rescued by reintroduction of Tks4, whereas only podosome formation, but not ECM degradation, was rescued by overexpression of Tks5. The tyrosine phosphorylation sites of Tks4 were required for efficient rescue. Furthermore, in the absence of Tks4, membrane type-1 matrix metalloproteinase (MT1-MMP) was not recruited to the incomplete podosomes. These findings suggest that Tks4 and Tks5 have overlapping, but not identical, functions, and implicate Tks4 in MT1-MMP recruitment and ECM degradation.

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“…Specifically, calpain-mediated proteolysis of talin and FAK can be rate-limiting steps in focal adhesion turnover (Franco et al 2004;Chan et al 2010). Calpains have also been implicated in the disassembly of podosomes in dendritic cells (Calle et al 2006) and invadopodia in cancer cells (Cortesio et al 2008), suggesting that calpains regulate the dynamics of diverse types of adhesions.…”

Section: Disassembly and Retraction Of The Cell's Rearmentioning

confidence: 99%

Integrins in Cell Migration

Chan

Cortesio

Huttenlocher

2007

Methods in Enzymology

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Integrin-based adhesion has served as a model for studying the central role of adhesion in migration. In this article, we outline modes of migration, both integrin-dependent and -independent in vitro and in vivo. We next discuss the roles of adhesion contacts as signaling centers and linkages between the ECM and actin that allows adhesions to serve as traction sites. This includes signaling complexes that regulate migration and the interplay among adhesion, signaling, and pliability of the substratum. Finally, we address mechanisms of adhesion assembly and disassembly and the role of adhesion in cellular polarity.

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Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion

Cited by 162 publications

References 49 publications

Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling

Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling

The Novel Adaptor Protein Tks4 (SH3PXD2B) Is Required for Functional Podosome Formation

Integrins in Cell Migration

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