A proximity-labeling proteomic approach to investigate invadopodia molecular landscape in breast cancer cells

Thuault, Sylvie; Mamelonet, Claire; Salameh, Joëlle; Ostacolo, Kevin; Chanez, Brice; Salaün, Danièle; Baudelet, Emilie; Audebert, Stéphane; Camoin, Luc; Badache, Ali

doi:10.1038/s41598-020-63926-4

Cited by 16 publications

(14 citation statements)

References 87 publications

(114 reference statements)

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“…They also showed that, when constitutively active SRC is present, TKS4 accumulates in podosomes (actin-rich membrane protrusions involved in cell motility, see below) while forming a complex with SRC and cortactin [9]. TKS5 has also been reported to bind cortactin and other proteins important in the regulation of actin cytoskeleton assembly, including N-WASP, non-catalytic region of tyrosine kinase adaptor protein (NCK), and GRB2 (for a full list, see Table 1b) [10,29,52,78,79].…”

Section: Unknownmentioning

confidence: 99%

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Kudlik

Takács

Radnai

et al. 2020

IJMS

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Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. Until recently, TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development, among others. However, a number of novel functions have been discovered for these molecules in recent years. In this review, we attempt to cover the diverse nature of the TKS molecules by discussing their structure, regulation by SRC kinase, relevant signaling pathways, and interaction partners, as well as their involvement in cellular processes, including migration, invasion, differentiation, and adipose tissue and bone homeostasis. We also describe related pathologies and the established mouse models.

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Section: Unknownmentioning

confidence: 99%

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Kudlik

Takács

Radnai

et al. 2020

IJMS

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“…Coverslips coated with Oregon Green 488-conjugated gelatin (Life technologies, ThermoFisher) were prepared as described in Thuault et al [ 30 ]. After seeding for 4 h on gelatin-coated coverslips rehydrated in complete growth medium for 1 h before use, cells were fixed with a solution of 4% formaldehyde in PBS, permeabilized with 0.1% Triton X-100, and blocked with 1% BSA.…”

Section: Methodsmentioning

confidence: 99%

EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Chanez

Ostacolo

Badache

et al. 2021

Cells

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Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.

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“…Since protein expression and function are influenced by post-transcriptional regulations, DNA/RNA sequencing cannot provide a full view of the process of metastases. Current proteomic technologies were used to identify and characterize the molecular components of the invadopodia linked to the metastatic progression of BC cells [182]. High throughput protein arrays have also been used to compare proteins expression between normal and malignant breast tissue with some interesting findings [183].…”

Section: Future Perspectivesmentioning

confidence: 99%

Functional Genomic Analysis of Breast Cancer Metastasis: Implications for Diagnosis and Therapy

Song

Chouchane

et al. 2021

Cancers

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Breast cancer (BC) is one of the most diagnosed cancers worldwide and is the second cause of cancer related death in women. The most frequent cause of BC-related deaths, like many cancers, is metastasis. However, metastasis is a complicated and poorly understood process for which there is a shortage of accurate prognostic indicators and effective treatments. With the rapid and ever-evolving development and application of genomic sequencing technologies, many novel molecules were identified that play previously unappreciated and important roles in the various stages of metastasis. In this review, we summarize current advancements in the functional genomic analysis of BC metastasis and discuss about the potential prognostic and therapeutic implications from the recent genomic findings.

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A proximity-labeling proteomic approach to investigate invadopodia molecular landscape in breast cancer cells

Cited by 16 publications

References 87 publications

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Functional Genomic Analysis of Breast Cancer Metastasis: Implications for Diagnosis and Therapy

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