ArticleCancer cell international2019
Overexpression and Tyr421-phosphorylation of cortactin is induced by three-dimensional spheroid culturing and contributes to migration and invasion of pancreatic ductal adenocarcinoma (PDAC) cells.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
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- A promising breakthrough in pancreatic cancer research: The potential of spheroids as 3D models.BioImpacts : BI · 2025Review
- Dynamic modulation of matrix adhesiveness induces epithelial-to-mesenchymal transition in prostate cancer cells in 3D.Biomaterials · 2023Article
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- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
- A Proteomic Approach to Study the Biological Role of Hepatitis C Virus Protein Core+1/ARFP.Viruses · 2022Article
- Gab1 regulates invadopodia and autocrine VEGF through SHP2/ERK1/2 in hilar cholangiocarcinoma cells.American journal of translational research · 2022Article
- A standardized extract of culturedOncology letters · 2021Article
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- Focal adhesion kinase confers pro-migratory and antiapoptotic properties and is a potential therapeutic target in Ewing sarcoma.Molecular oncology · 2020Article
- Review
- Cortactin in Epithelial-Mesenchymal Transition.Frontiers in cell and developmental biology · 2020Review
- Expression of Formin-like 2 and cortactin in gallbladder adenocarcinoma and their clinical significance.International journal of clinical and experimental pathology · 2020Article
- CRISPR Cas9 in Pancreatic Cancer Research.Frontiers in cell and developmental biology · 2019Review
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10 authors at 2 institutions in 1 country.
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Abstract
backgroundThe nucleation-promoting factor cortactin is expressed and promotes tumor progression and metastasis in various cancers. However, little is known about the biological role of cortactin in the progression of pancreatic ductal adenocarcinoma (PDAC).
methodsCortactin and phosphorylated cortactin (Y421) were investigated immunohistochemically in 66 PDAC tumor specimens. To examine the functional role of cortactin in PDAC, we modulated cortactin expression by establishing two cortactin knockout cell lines (Panc-1 and BxPC-3) with CRISPR/Cas9 technique. Cortactin knockout was verified by immunoblotting and immunofluorescence microscopy and functional effects were determined by cell migration and invasion assays. A proteomic screening approach was performed to elucidate potential binding partners of cortactin.
resultsImmunohistochemically, we observed higher cortactin expression and Tyr421-phosphorylation in PDAC metastases compared to primary tumor tissues. In PDAC cell lines Panc-1 and BxPC-3, knockdown of cortactin impaired migration and invasion, while cell proliferation was not affected. Three-dimensional spheroid culturing as a model for collective cell migration enhanced cortactin expression and Tyr421-phosphorylation. The activation of cortactin as well as the migratory capacity of PDAC cells could significantly be reduced by dasatinib, a Src family kinase inhibitor. Finally, we identified gelsolin as a novel protein interaction partner of cortactin in PDAC.
conclusionOur data provides evidence that cohesive cell migration induces cortactin expression and phosphorylation as a prerequisite for the gain of an invasive, pro-migratory phenotype in PDAC that can effectively be targeted with dasatinib.
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