ArticleBMC cancer2013
Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 58 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
- Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520.Targeted oncology · 2019Trial
- Multifaceted Roles of Bcl-2 Family Proteins: Regulatory Roles in Apoptosis, Physiological Functions, and Therapeutic Potential.Current medical science · 2025Review
- Recent advances in focal adhesion kinase (FAK)-targeting antitumor agents.RSC advances · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Actin-Dependent Mechanism of Tumor Progression Induced by a Dysfunction of p53 Tumor Suppressor.Cancers · 2024Article
- FAK Drives Resistance to Therapy in HPV-Negative Head and Neck Cancer in a p53-Dependent Manner.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- New Insights on the Nuclear Functions and Targeting of FAK in Cancer.International journal of molecular sciences · 2022Review
- FAK in Cancer: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2022Review
- Computational Design of Peptides with Improved Recognition of the Focal Adhesion Kinase FAT Domain.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Focal adhesion kinase inhibitors, a heavy punch to cancer.Discover oncology · 2021Review
- Article
- FAK displacement from focal adhesions: a promising strategy to target processes implicated in cancer progression and metastasis.Cell communication and signaling : CCS · 2021Article
- Azaadamantanes, a New Promising Scaffold for Medical Chemistry.Russian journal of bioorganic chemistry · 2021Article
- FAK Signaling in Rhabdomyosarcoma.International journal of molecular sciences · 2020Review
- Structure-Based Virtual Screening, Synthesis and Biological Evaluation of Potential FAK-FAT Domain Inhibitors for Treatment of Metastatic Cancer.Molecules (Basel, Switzerland) · 2020Article
- Targeting the Extra-Cellular Matrix-Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors.Frontiers in oncology · 2020Review
- Role of Focal Adhesion Kinase in Small-Cell Lung Cancer and Its Potential as a Therapeutic Target.Cancers · 2019Review
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundFocal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis.
methodsWe performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site.
resultsBy different assays in isogenic HCT116p53+/+ and HCT116 p53-/- cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53+/+ but not in HCT116 p53-/- xenografts in vivo. In addition, R2 sensitized HCT116p53+/+ cells to doxorubicin and 5-fluorouracil.
conclusionsThus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches.
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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.