ArticleOncotarget2014
FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 41 citations in OpenAlex.
- Cytotoxic Effects of Sorafenib, Lapatinib, and Bevacizumab, Alone and in Combination, on Medullary Thyroid Carcinoma Cells.Current oncology (Toronto, Ont.) · 2025Article
- Growth arrest specific-6 and angiotoxin receptor-like signaling drive oral regenerative wound repair.Science translational medicine · 2025Article
- Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma.Biomolecules · 2024Article
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- Tumor removal limits prostate cancer cell dissemination in bone and osteoblasts induce cancer cell dormancy through focal adhesion kinase.Journal of experimental & clinical cancer research : CR · 2023Article
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- Focal adhesion kinase inhibitors, a heavy punch to cancer.Discover oncology · 2021Review
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- Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model.International journal of molecular sciences · 2021Article
- BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Coupling to substrate adhesions drives the maturation of muscle stress fibers into myofibrils within cardiomyocytes.Molecular biology of the cell · 2020Article
- Influenza Virus Infections and Cellular Kinases.Viruses · 2019Review
- Monitoring focal adhesion kinase phosphorylation dynamics in live cells.The Analyst · 2017Article
- Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo.Cancer science · 2017Article
- Multicellular spheroids from normal and neoplastic thyroid tissues as a suitable model to test the effects of multikinase inhibitors.Oncotarget · 2017Article
- Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.Frontiers in oncology · 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
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- In vitro activities of hexaazatrinaphthylenes against Leishmania spp.Antimicrobial agents and chemotherapy · 2015Article
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Focal adhesion kinase (FAK) is up-regulated in thyroid cancer and small molecule FAK scaffolding inhibitor, Y15, was shown to decrease cancer growth in vitro and in vivo. We sought to test the effectiveness of Y15 in thyroid cancer cell lines, profile gene expression with Y15 compared with clinical trial FAK inhibitor PF-04554878, and use Y15 in novel drug combinations. Cell viability was decreased in a dose dependent manner in four thyroid cancer cell lines with Y15 and with higher doses in PF-04554878. Y397 FAK and total FAK were decreased with Y15 and decreased less with PF-04554878. Detachment and necrosis were increased in a dose-dependent manner in all cell lines with Y15. Clonogenicity was decreased in a dose-dependent manner for both Y15 and PF-04554878. We compared gene profiles between papillary thyroid cell lines, TPC1, BCPAP and K1, and 380, 109, and 74 genes were significantly >2-fold changed with Y15 treatment, respectively. Common up-regulated genes were involved in apoptosis, cell cycle, transcription and heat shock; down-regulated genes were involved in cell cycle, cell-to-cell interactions, and cancer stem cell markers. We also compared gene profiles of TT cells treated with Y15 versus PF-04554878. Y15 caused 144 genes to change over 4 fold and PF-04554878 caused 208 gene changes >4-fold (p<0.05). Among genes changed 4 fold, 11 were shared between the treatments, including those involved in metabolism, cell cycle, migration and transcription. Y15 demonstrated synergy with PF-04554878 in TT cells and also synergy with Cabozantinib, Sorafenib, Pazopanib, and strong synergy with Sunitinib in resistant K1 cells. This report revealed the biological effect of Y15 inhibitor, detected the unique and common gene signature profiles in response to Y15 in 4 different thyroid cancer cell lines, demonstrated differential response changes with Y15 and PF-04554878 treatment, and showed the synergy of Y15 with PF-04554878, Cabozantinib, Sorafenib, Pazopanib, and Sunitinib.
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