ArticleScience signaling2012
Network analysis of the focal adhesion to invadopodia transition identifies a PI3K-PKCα invasive signaling axis.
Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 77 citations in OpenAlex.
- Delivery of Pleckstrin-Homology Domains Suppresses PI3K/Akt Signaling and Breast Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integration of machine learning to reveal the correlation between ferroptosis and M2 macrophages in head and neck squamous cell carcinoma.Discover oncology · 2025Article
- Invadopodia in cancer metastasis: dynamics, regulation, and targeted therapies.Journal of translational medicine · 2025Review
- The oncolytic avian reovirus p17 protein suppresses invadopodia formation via disruption of TKs5 complexes and oncogenic signaling pathways.Frontiers in cellular and infection microbiology · 2025Article
- Article
- The impact of lipidome on breast cancer: a Mendelian randomization study.Lipids in health and disease · 2024Article
- Protein dynamics at invadopodia control invasion-migration transitions in melanoma cells.Cell death & disease · 2023Article
- ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia.The Journal of cell biology · 2023Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Research for Expression and Prognostic Value of GABRD in Colon Cancer and Coexpressed Gene Network Construction Based on Data Mining.Computational and mathematical methods in medicine · 2021Article
- PTEN and Other PtdIns(3,4,5)PInternational journal of molecular sciences · 2020Review
- Intersection of TKS5 and FGD1/CDC42 signaling cascades directs the formation of invadopodia.The Journal of cell biology · 2020Article
- Septin2 mediates podosome maturation and endothelial cell invasion associated with angiogenesis.The Journal of cell biology · 2020Article
- Article
- Tail domains of myosin-1e regulate phosphatidylinositol signaling and F-actin polymerization at the ventral layer of podosomes.Molecular biology of the cell · 2019Article
- Matrix stiffness mechanically conditions EMT and migratory behavior of oral squamous cell carcinoma.Journal of cell science · 2019Article
- BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells.Scientific reports · 2018Article
- Expression of human papillomavirus oncoproteins E6 and E7 inhibits invadopodia activity but promotes cell migration in HPV-positive head and neck squamous cell carcinoma cells.Cancer reports (Hoboken, N.J.) · 2018Article
- Crosstalk between PKCα and PI3K/AKT Signaling Is Tumor Suppressive in the Endometrium.Cell reports · 2018Article
- miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
In cancer, deregulated signaling can produce an invasive cellular phenotype. We modeled the invasive transition as a theoretical switch between two cytoskeletal structures: focal adhesions and extracellular matrix-degrading invadopodia. We constructed molecular interaction networks of each structure and identified upstream regulatory hubs through computational analyses. We compared these regulatory hubs to the status of signaling components from head and neck carcinomas, which led us to analyze phosphatidylinositol 3-kinase (PI3K) and protein kinase C α (PKCα). Consistent with previous studies, PI3K activity promoted both the formation and the activity of invadopodia. We found that PI3K induction of invadopodia was increased by overexpression of SH2 (Src homology 2) domain-containing inositol 5'-phosphatase 2 (SHIP2), which converts the phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] that is produced by PI3K activity to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P(2)], which is believed to promote invadopodia formation. Knockdown of PKCα had divergent effects on invadopodia formation, depending on the status of PI3K. Loss of PKCα inhibited invadopodia formation in cells with wild-type PI3K pathway status. Conversely, in cells with constitutively active PI3K (through activating PI3K mutants or lacking the endogenous opposing enzyme PTEN), PKCα knockdown increased invadopodia formation. Mechanistic studies revealed a negative feedback loop from PKCα that dampened PI3K activity and invasive behavior in cells with genetic hyperactivation of the PI3K pathway. These studies demonstrated the potential of network modeling as a discovery tool and identified PI3K and PKCα as interacting regulators of invasive behavior.
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Registered trials
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.