ArticleJournal of cell science2012
Met receptor tyrosine kinase signals through a cortactin-Gab1 scaffold complex, to mediate invadopodia.
Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- Nuclear transport of phosphorylated LanCL2 promotes invadopodia formation and tumor progression of glioblastoma by activating STAT3/Cortactin signaling.Journal of advanced research · 2025Article
- Identification of Novel Gene Signature Predicting Lymph Node Metastasis in Papillary Thyroid Cancer via Bioinformatics Analysis and in vitro Validation.International journal of general medicine · 2025Article
- Cross-talk between gastric cancer and hepatic stellate cells promotes invadopodia formation during liver metastasis.Cancer science · 2024Article
- AberrantCells · 2024Review
- PLXDC2 enhances invadopodium formation to promote invasion and metastasis of gastric cancer cells via interacting with PTP1B.Clinical & experimental metastasis · 2022Article
- Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.Neoplasia (New York, N.Y.) · 2022Article
- Gab1 regulates invadopodia and autocrine VEGF through SHP2/ERK1/2 in hilar cholangiocarcinoma cells.American journal of translational research · 2022Article
- The role of MET in chemotherapy resistance.Oncogene · 2021Review
- Receptor Tyrosine Kinase Signaling and Targeting in Glioblastoma Multiforme.International journal of molecular sciences · 2021Review
- RET isoforms contribute differentially to invasive processes in pancreatic ductal adenocarcinoma.Oncogene · 2020Article
- The AKT-independent MET-V-ATPase-MTOR axis suppresses liver cancer vaccination.Signal transduction and targeted therapy · 2020Article
- Cortactin function in invadopodia.Small GTPases · 2020Review
- FER mediated HGF-independent regulation of HGFR/MET activates RAC1-PAK1 pathway to potentiate metastasis in ovarian cancer.Small GTPases · 2020Article
- Enhanced Autophagy in GAB1-Deficient Vascular Endothelial Cells Is Responsible for Atherosclerosis Progression.Frontiers in physiology · 2020Article
- Splicing Busts a Move: Isoform Switching Regulates Migration.Trends in cell biology · 2020Review
- Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation.Frontiers in cell and developmental biology · 2020Review
- Tailoring subtractive cell biopanning to identify diffuse gastric adenocarcinoma-associated antigens via human scFv antibodies.Immunology · 2020Article
- Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells.Journal of cellular and molecular medicine · 2019Article
- HGF-induced migration depends on the PI(3,4,5)PThe Journal of cell biology · 2019Article
- Combination of Selected MET and EGFR Inhibitors Decreases Melanoma Cells' Invasive Abilities.Frontiers in pharmacology · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Invasive carcinoma cells form actin-rich matrix-degrading protrusions called invadopodia. These structures resemble podosomes produced by some normal cells and play a crucial role in extracellular matrix remodeling. In cancer, formation of invadopodia is strongly associated with invasive potential. Although deregulated signals from the receptor tyrosine kinase Met (also known as hepatocyte growth factor are linked to cancer metastasis and poor prognosis, its role in invadopodia formation is not known. Here we show that stimulation of breast cancer cells with the ligand for Met, hepatocyte growth factor, promotes invadopodia formation, and in aggressive gastric tumor cells where Met is amplified, invadopodia formation is dependent on Met activity. Using both GRB2-associated-binding protein 1 (Gab1)-null fibroblasts and specific knockdown of Gab1 in tumor cells we show that Met-mediated invadopodia formation and cell invasion requires the scaffold protein Gab1. By a structure-function approach, we demonstrate that two proline-rich motifs (P4/5) within Gab1 are essential for invadopodia formation. We identify the actin regulatory protein, cortactin, as a direct interaction partner for Gab1 and show that a Gab1-cortactin interaction is dependent on the SH3 domain of cortactin and the integrity of the P4/5 region of Gab1. Both cortactin and Gab1 localize to invadopodia rosettes in Met-transformed cells and the specific uncoupling of cortactin from Gab1 abrogates invadopodia biogenesis and cell invasion downstream from the Met receptor tyrosine kinase. Met localizes to invadopodia along with cortactin and promotes phosphorylation of cortactin. These findings provide insights into the molecular mechanisms of invadopodia formation and identify Gab1 as a scaffold protein involved in this process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.