Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway

Magalhaes, Marco; Larson, Daniel R.; Mader, Christopher C.; Bravo‐Cordero, Jose Javier; Gil-Henn, Hava; Oser, Matthew G.; Chen, Xiaoming; Koleske, Anthony J.; Condeelis, John S.

doi:10.1083/jcb.201103045

Cited by 191 publications

(234 citation statements)

References 86 publications

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“…3E). Cortactin binding to cofilin inhibits cofilin severing of actin filaments (12,13). We observe a similar effect, but with significantly higher concentrations of cofilin than cortactin suggesting an alternative mechanism, possibly mediated through structural changes to the actin filament.…”

Section: Discussionsupporting

confidence: 60%

“…For example, Arg is present at 0.4 -0.6 M in dendritic spines, and cortactin concentrations may be as high as 4 M within breast cancer cell invadopodia (12,17,41). Dendritic spines in Arg-deficient neurons exhibit a loss of cortactin, reduced actin content, morphological changes, and loss of stability both in culture and in vivo (7,32).…”

Section: Discussionmentioning

confidence: 99%

“…One important Arg substrate is cortactin, an actin-binding protein that stimulates the Arp2/3 complex to nucleate actin filament branches (9 -11). Cortactin also stabilizes actin filament branches (9) and inhibits actin filament severing by cofilin (12,13).…”

mentioning

confidence: 99%

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Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin

Courtemanche

Gifford

Simpson

et al. 2015

Journal of Biological Chemistry

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Background: Arg/Abl2 has two actin-binding domains, but how they influence actin filaments was unknown. Results: Arg and cortactin cooperatively stabilize actin filaments; Arg enhances Arp2/3 complex activation and stimulates severing by cofilin. Conclusion: Arg directly regulates actin filament stability, branching, and severing, which are modulated by cortactin. Significance: These activities may underlie the control of actin-based cellular structures by Arg.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin

Courtemanche

Gifford

Simpson

et al. 2015

Journal of Biological Chemistry

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“…Recent evidence for repeating cycles of protrusion and retraction of invadopodia was indeed described. 150 The three functional domains of invadopodia, which are discussed above, are in fact, packed into one coherent structure presented in the transmission electron micrograph, shown in Figure 3. Transmission electron micrographs of invadopodia were shown previously in several cell types.…”

Section: An Integrated View Of Invadopodia's Functional Architecturementioning

confidence: 99%

The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion

Revach

Geiger

2013

Cell Adhesion & Migration

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“…Coverslips are coated with a mixture of 0.2% gelatin and TRITC ester (8:1 ratio) for HCC 1806 cells as previously described (26). For MDA-MB-231, coverslips with TRITC-fibronectin were prepared, as previously described (15).…”

Section: Ecm Degradation Assaysmentioning

confidence: 99%

Endophilin A2 Promotes TNBC Cell Invasion and Tumor Metastasis

Baldassarre

Watt

Truesdell

et al. 2015

Molecular Cancer Research

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Triple-negative breast cancers (TNBCs) are highly aggressive cancers that lack targeted therapies. However, EGFR is frequently activated in a subset of TNBCs and represents a viable clinical target. Because the endocytic adaptor protein Endophilin A2 (SH3GL1/Endo II) has been implicated in EGFR internalization, we investigated Endo II expression and function in human TNBCs. Endo II expression was high in several TNBC cells compared with normal breast epithelial cells. Stable knockdown (KD) of Endo II was achieved in two TNBC cell lines, and although cell viability was unaffected, defects in receptor-mediated endocytosis were observed. EGFR signaling to Erk and Akt kinases was impaired in Endo II KD cells, and this correlated with reduced rates of EGFR internalization and cell motility. Endo II KD cells also displayed defects in three dimensional (3D) cell invasion, and this correlated with impaired extracellular matrix degradation and internalization of MT1-MMP. Endo II silencing also caused a significant reduction in TNBC tumor growth and lung metastasis in mammary orthotopic tumor xenograft assays. In human breast tumor specimens, Endo II expression was highest in TNBC tumors compared with other subtypes, and at the level of gene expression, high Endo II was associated with reduced relapse-free survival in patients with basal-like breast cancers. Together, these results identify a positive role for Endo II in TNBC tumor metastasis and a potential link with poor prognosis.Implications: Endophilin A2 and related adaptor proteins represent important signaling hubs to target in metastatic cancers. Mol Cancer Res; 13(6); 1044-55. Ó2015 AACR.

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Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway

Abstract: Cortactin phosphorylation induces recruitment of the sodium-hydrogen exchanger NHE1 to invadopodia, resulting in pH changes that regulate cortactin-cofilin binding and invadopodium dynamics.

Cited by 191 publications

References 86 publications

Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin

Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin

The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion

Endophilin A2 Promotes TNBC Cell Invasion and Tumor Metastasis

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