ArticleBMC cancer2009
The direct effect of focal adhesion kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis.
Article in BMC cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 66 citations in OpenAlex.
- Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- NAT10 regulates tumor progression and immune microenvironment in pancreatic ductal adenocarcinoma via the N4-acetylated LAMB3-mediated FAK/ERK pathway.Cancer communications (London, England) · 2025Article
- GSK3 acts as a switch for transcriptional programs in a model of low-grade gliomagenesis.Acta neuropathologica communications · 2025Article
- Structure-based discovery of hydrocarbon-stapled paxillin peptides that block FAK scaffolding in cancer.Nature communications · 2025Article
- SPP1 promotes tumor progression in esophageal carcinoma by activating focal adhesion pathway.Journal of gastrointestinal oncology · 2024Article
- Development and Characterization of Selective FAK Inhibitors and PROTACs with In Vivo Activity.Chembiochem : a European journal of chemical biology · 2023Article
- Linc00662 mAmerican journal of cancer research · 2023Article
- Induction of Apoptosis and Effect on the FAK/AKT/mTOR Signal Pathway by Evodiamine in Gastric Cancer Cells.Current issues in molecular biology · 2022Article
- FAK inhibitors as promising anticancer targets: present and future directions.Future medicinal chemistry · 2021Review
- Review
- Extracellular vesicles from young women's breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach.Breast cancer research : BCR · 2020Observational
- Exosomal L1CAM Stimulates Glioblastoma Cell Motility, Proliferation, and Invasiveness.International journal of molecular sciences · 2019Article
- Article
- Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma.Cancer biology & therapy · 2018Article
- Rescue of PFOS-induced human Sertoli cell injury by overexpressing a p-FAK-Y407E phosphomimetic mutant.Scientific reports · 2017Article
- Focal adhesion kinase maintains, but not increases the adhesion of dental pulp cells.Human cell · 2017Article
- FAK and paxillin, two potential targets in pancreatic cancer.Oncotarget · 2016Review
- Tumor Necrosis Factor-α (TNFα)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death.The Journal of biological chemistry · 2015Article
- Focal adhesion kinase and p53 synergistically decrease neuroblastoma cell survival.The Journal of surgical research · 2015Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis.
methodsTo study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible) system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD), and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors.
resultsInduction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p < 0.05) by FAKsiRNA.
conclusionThus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal specific expression of genes affected by silencing of FAK.
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