Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction
Abstract
1. Introduction
2. FAK and Mechanotransduction
3. FAK Alterations in Pathologies Associated with Altered Mechanotransduction
3.1. FAK Network and ECM Stiffness
3.2. FAK in Fibrosis and Inflammation
3.3. FAK Involvement in Endothelial Cell Mechanotransduction and Function
3.4. FAK in Heart Disease
3.5. FAK-Mediated Mechanotransduction in Bone Cells
4. Therapeutic Implications for Targeting Mechanoactivator FAK
5. Conclusions
Funding
Conflicts of Interest
Abbreviations
CAV | Caveolin-1 |
CSF-1R | Colony Stimulating Factor 1 Receptor |
ECM | Extracellular Matrix |
ERK | Extracellular-Related Kinase |
FA | Focal Adhesion |
FAK | Focal Adhesion Kinase |
FSS | Fluid Shear Stress |
MCP-1 | Monocyte Chemoattractant Protein-1 |
M-CSF | Macrophage Colony-Stimulating Factor |
MSCs | Mesenchymal Stromal Cells |
NO | Nitric Oxide |
PKG | Protein-Kinase G |
Pyk2 | Protein Tyrosine Kinase 2β |
Runx-2 | Runt-Related Transcription Factor 2 |
Sox9 | SRY-Box Transcription Factor 9 |
VE-cadherin | Vascular Endothelial Cadherin |
References
- Clippinger, S.R.; Cloonan, P.E.; Greenberg, L.; Ernst, M.; Stump, W.T.; Greenberg, M.J. Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy. Proc. Natl. Acad. Sci. USA 2019, 116, 17831–17840. [Google Scholar] [CrossRef] [PubMed]
- Ingber, D.E. Mechanobiology and diseases of mechanotransduction. Ann. Med. 2003, 35, 564–577. [Google Scholar] [CrossRef] [PubMed]
- Miroshnikova, Y.A.; Hammesfahr, T.; Wickstrom, S.A. Cell biology and mechanopathology of laminopathic cardiomyopathies. J. Cell Biol. 2019, 218, 393–394. [Google Scholar] [CrossRef] [PubMed]
- Kechagia, J.Z.; Ivaska, J.; Roca-Cusachs, P. Integrins as biomechanical sensors of the microenvironment. Nat. Rev. Mol. Cell Biol. 2019, 20, 457–473. [Google Scholar] [CrossRef]
- Martino, F.; Perestrelo, A.R.; Vinarsky, V.; Pagliari, S.; Forte, G. Cellular Mechanotransduction: From Tension to Function. Front. Physiol. 2018, 9, 824. [Google Scholar] [CrossRef]
- Cohen, L.A.; Guan, J.L. Mechanisms of focal adhesion kinase regulation. Curr. Cancer Drug Targets 2005, 5, 629–643. [Google Scholar] [CrossRef]
- Parsons, J.T. Focal adhesion kinase: The first ten years. J. Cell Sci. 2003, 116, 1409–1416. [Google Scholar] [CrossRef]
- Kanner, S.B.; Reynolds, A.B.; Vines, R.R.; Parsons, J.T. Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases. Proc. Natl. Acad. Sci. USA 1990, 87, 3328–3332. [Google Scholar] [CrossRef]
- Kornberg, L.J.; Earp, H.S.; Turner, C.E.; Prockop, C.; Juliano, R.L. Signal transduction by integrins: Increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins. Proc. Natl. Acad. Sci. USA 1991, 88, 8392–8396. [Google Scholar] [CrossRef]
- Seong, J.; Tajik, A.; Sun, J.; Guan, J.-L.; Humphries, M.J.; Craig, S.E.; Shekaran, A.; García, A.J.; Lu, S.; Lin, M.Z.; et al. Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins. Proc. Natl. Acad. Sci. USA 2013, 110, 19372–19377. [Google Scholar] [CrossRef]
- Horton, E.R.; Humphries, J.D.; James, J.; Jones, M.C.; Askari, J.A.; Humphries, M.J. The integrin adhesome network at a glance. J. Cell Sci. 2016, 129, 4159–4163. [Google Scholar] [CrossRef] [PubMed]
- Ciobanasu, C.; Wang, H.; Henriot, V.; Mathieu, C.; Fente, A.; Csillag, S.; Vigouroux, C.; Faivre, B.; Le Clainche, C. Integrin-bound talin head inhibits actin filament barbed-end elongation. J. Biol. Chem. 2018, 293, 2586–2596. [Google Scholar] [CrossRef] [PubMed]
- Klapholz, B.; Brown, N.H. Talin—The master of integrin adhesions. J. Cell Sci. 2017, 130, 2435–2446. [Google Scholar] [CrossRef] [PubMed]
- Critchley, D.R.; Gingras, A.R. Talin at a glance. J. Cell Sci. 2008, 121, 1345–1347. [Google Scholar] [CrossRef] [PubMed]
- Bays, J.L.; DeMali, K.A. Vinculin in cell-cell and cell-matrix adhesions. Cell Mol. Life Sci. 2017, 74, 2999–3009. [Google Scholar] [CrossRef] [PubMed]
- Kadrmas, J.L.; Beckerle, M.C. The LIM domain: From the cytoskeleton to the nucleus. Nat. Rev. Mol. Cell Biol. 2004, 5, 920–931. [Google Scholar] [CrossRef]
- Qin, R.; Schmid, H.; Muenzberg, C.; Maass, U.; Krndija, D.; Adler, G.; Seufferlein, T.; Liedert, A.; Ignatius, A.; Oswald, F.; et al. Phosphorylation and turnover of paxillin in focal contacts is controlled by force and defines the dynamic state of the adhesion site. Cytoskeleton 2015, 72, 101–112. [Google Scholar] [CrossRef]
- Bradbury, P.; Turner, K.; Mitchell, C.; Griffin, K.R.; Middlemiss, S.; Lau, L.; Dagg, R.; Taran, E.; Cooper-White, J.; Fabry, B.; et al. The focal adhesion targeting domain of p130Cas confers a mechanosensing function. J. Cell Sci. 2017, 130, 1263–1273. [Google Scholar] [CrossRef]
- Bauer, M.S.; Baumann, F.; Daday, C.; Redondo, P.; Durner, E.; Jobst, M.A.; Milles, L.F.; Mercadante, D.; Pippig, D.A.; Gaub, H.E.; et al. Structural and mechanistic insights into mechanoactivation of focal adhesion kinase. Proc. Natl. Acad. Sci. USA 2019, 116, 6766–6774. [Google Scholar] [CrossRef]
- Zhou, D.W.; Lee, T.T.; Weng, S.; Fu, J.; Garcia, A.J. Effects of substrate stiffness and actomyosin contractility on coupling between force transmission and vinculin-paxillin recruitment at single focal adhesions. Mol. Biol. Cell 2017, 28, 1901–1911. [Google Scholar] [CrossRef]
- Jung, O.; Choi, S.; Jang, S.-B.; Lee, S.-A.; Lim, S.-T.; Choi, Y.-J.; Kim, H.-J.; Kim, D.-H.; Kwak, T.K.; Kang, M.; et al. Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells. J. Cell Sci. 2012, 125, 5960–5973. [Google Scholar] [CrossRef] [PubMed]
- Bell, S.; Terentjev, E.M. Focal Adhesion Kinase: The Reversible Molecular Mechanosensor. Biophys. J. 2017, 112, 2439–2450. [Google Scholar] [CrossRef]
- Levental, K.R.; Yu, H.; Kass, L.; Lakins, J.N.; Egeblad, M.; Erler, J.T.; Fong, S.F.; Csiszar, K.; Giaccia, A.; Weninger, W.; et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009, 139, 891–906. [Google Scholar] [CrossRef] [PubMed]
- Rens, E.G.; Merks, R.M.H. Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics. iScience 2020, 23, 101488. [Google Scholar] [CrossRef]
- Wei, W.C.; Lin, H.H.; Shen, M.R.; Tang, M.J. Mechanosensing machinery for cells under low substratum rigidity. Am. J. Physiol. Cell Physiol. 2008, 295, C1579–C1589. [Google Scholar] [CrossRef] [PubMed]
- Yeh, Y.C.; Ling, J.Y.; Chen, W.C.; Lin, H.H.; Tang, M.J. Mechanotransduction of matrix stiffness in regulation of focal adhesion size and number: Reciprocal regulation of caveolin-1 and beta1 integrin. Sci. Rep. 2017, 7, 15008. [Google Scholar] [CrossRef] [PubMed]
- Radel, C.; Rizzo, V. Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am. J. Physiol. Heart Circ. Physiol. 2005, 288, H936–H945. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Grande-García, A.; Echarri, A.; De Rooij, J.; Alderson, N.B.; Waterman-Storer, C.M.; Valdivielso, J.M.; Del Pozo, M.A. Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. J. Cell Biol. 2007, 177, 683–694. [Google Scholar] [CrossRef]
- Moreno-Vicente, R.; Pavón, D.M.; Martín-Padura, I.; Català-Montoro, M.; Díez-Sánchez, A.; Quílez-Álvarez, A.; López, J.A.; Sánchez-Álvarez, M.; Vázquez, J.; Strippoli, R.; et al. Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP. Cell Rep. 2018, 25, 1622–1635. [Google Scholar] [CrossRef]
- Joshi, B.; Bastiani, M.; Strugnell, S.S.; Boscher, C.; Parton, R.G.; Nabi, I.R. Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation. J. Cell Biol. 2012, 199, 425–435. [Google Scholar] [CrossRef]
- Wong, T.H.; Dickson, F.H.; Timmins, L.R.; Nabi, I.R. Tyrosine phosphorylation of tumor cell caveolin-1: Impact on cancer progression. Cancer Metastasis Rev. 2020, 39, 455–469. [Google Scholar] [CrossRef] [PubMed]
- Swift, J.; Ivanovska, I.L.; Buxboim, A.; Harada, T.; Dingal, P.C.D.P.; Pinter, J.; Pajerowski, J.D.; Spinler, K.R.; Shin, J.-W.; Tewari, M.; et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 2013, 341, 1240104. [Google Scholar] [CrossRef] [PubMed]
- Irianto, J.; Pfeifer, C.R.; Ivanovska, I.L.; Swift, J.; Discher, D.E. Nuclear lamins in cancer. Cell Mol. Bioeng. 2016, 9, 258–267. [Google Scholar] [CrossRef] [PubMed]
- Urciuoli, E.; Petrini, S.; D’Oria, V.; Leopizzi, M.; Rocca, C.D.; Peruzzi, B. Nuclear Lamins and Emerin Are Differentially Expressed in Osteosarcoma Cells and Scale with Tumor Aggressiveness. Cancers 2020, 12, 443. [Google Scholar] [CrossRef]
- Kadaré, G.; Gervasi, N.; Brami-Cherrier, K.; Blockus, H.; El Messari, S.; Arold, S.T.; Girault, J.-A. Conformational dynamics of the focal adhesion targeting domain control specific functions of focal adhesion kinase in cells. J. Biol. Chem. 2015, 290, 478–491. [Google Scholar] [CrossRef]
- Lim, S.-T.; Chen, X.L.; Lim, Y.; Hanson, D.A.; Vo, T.-T.; Howerton, K.; Larocque, N.; Fisher, S.J.; Schlaepfer, D.D.; Ilic, D. Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol. Cell 2008, 29, 9–22. [Google Scholar] [CrossRef]
- Bagnato, G.; Leopizzi, M.; Urciuoli, E.; Peruzzi, B. Nuclear Functions of the Tyrosine Kinase Src. Int. J. Mol. Sci. 2020, 21, 2675. [Google Scholar] [CrossRef]
- Urciuoli, E.; Coletta, I.; Rizzuto, E.; De Vito, R.; Petrini, S.; D’Oria, V.; Pezzullo, M.; Milano, G.M.; Cozza, R.; Locatelli, F.; et al. Src nuclear localization and its prognostic relevance in human osteosarcoma. J. Cell. Physiol. 2018, 233, 1658–1670. [Google Scholar] [CrossRef]
- Chuang, H.-H.; Wang, P.-H.; Niu, S.-W.; Zhen, Y.-Y.; Huang, M.-S.; Hsiao, M.; Yang, C.-J. Inhibition of FAK Signaling Elicits Lamin A/C-Associated Nuclear Deformity and Cellular Senescence. Front. Oncol. 2019, 9, 22. [Google Scholar] [CrossRef]
- Aarabi, S.; Bhatt, K.A.; Shi, Y.; Paterno, J.; Chang, E.I.; Loh, S.A.; Holmes, J.W.; Longaker, M.T.; Yee, H.; Gurtner, G.C. Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J. 2007, 21, 3250–3261. [Google Scholar] [CrossRef]
- Wong, V.W.; Rustad, K.C.; Akaishi, S.; Sorkin, M.; Glotzbach, J.P.; Januszyk, M.; Nelson, E.R.; Levi, K.; Paterno, J.; Vial, I.N.; et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Nat. Med. 2011, 18, 148–152. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.B.; Dembo, M.; Hanks, S.K.; Wang, Y. Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl. Acad. Sci. USA 2001, 98, 11295–11300. [Google Scholar] [CrossRef] [PubMed]
- Januszyk, M.; Kwon, S.H.; Wong, V.W.; Padmanabhan, J.; Maan, Z.N.; Whittam, A.J.; Major, M.R.; Gurtner, G.C. The Role of Focal Adhesion Kinase in Keratinocyte Fibrogenic Gene Expression. Int. J. Mol. Sci. 2017, 18, 1915. [Google Scholar] [CrossRef] [PubMed]
- Lehoux, S.; Castier, Y.; Tedgui, A. Molecular mechanisms of the vascular responses to haemodynamic forces. J. Intern. Med. 2006, 259, 381–392. [Google Scholar] [CrossRef]
- Yang, S.; Gong, X.; Qi, Y.; Jiang, Z. Comparative study of variations in mechanical stress and strain of human blood vessels: Mechanical reference for vascular cell mechano-biology. Biomech. Model. Mechanobiol. 2020, 19, 519–531. [Google Scholar] [CrossRef]
- Zebda, N.; Dubrovskyi, O.; Birukov, K.G. Focal adhesion kinase regulation of mechanotransduction and its impact on endothelial cell functions. Microvasc. Res. 2012, 83, 71–81. [Google Scholar] [CrossRef]
- Nallanthighal, S.; Heiserman, J.P.; Cheon, D.J. The Role of the Extracellular Matrix in Cancer Stemness. Front. Cell Dev. Biol. 2019, 7, 86. [Google Scholar] [CrossRef]
- Barney, L.E.; Jansen, L.E.; Polio, S.R.; Galarza, S.; Lynch, M.E.; Peyton, S.R. The Predictive Link between Matrix and Metastasis. Curr. Opin. Chem. Eng. 2016, 11, 85–93. [Google Scholar] [CrossRef]
- Henke, E.; Nandigama, R.; Ergun, S. Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy. Front. Mol. Biosci. 2019, 6, 160. [Google Scholar] [CrossRef]
- Bordeleau, F.; Mason, B.N.; Lollis, E.M.; Mazzola, M.; Zanotelli, M.R.; Somasegar, S.; Califano, J.P.; Montague, C.; LaValley, D.J.; Huynh, J.; et al. Matrix stiffening promotes a tumor vasculature phenotype. Proc. Natl. Acad. Sci. USA 2017, 114, 492–497. [Google Scholar] [CrossRef]
- Guo, X.; Eitnier, R.A.; Beard, R.S., Jr.; Meegan, J.E.; Yang, X.; Aponte, A.M.; Wang, F.; Nelson, P.R.; Wu, M.H. Focal adhesion kinase and Src mediate microvascular hyperpermeability caused by fibrinogen- gammaC- terminal fragments. PLoS ONE 2020, 15, e0231739. [Google Scholar] [CrossRef] [PubMed]
- Francalanci, P.; Giovannoni, I.; De Stefanis, C.; Romito, I.; Grimaldi, C.; Castellano, A.; D’Oria, V.; Alaggio, R.; Alisi, A. Focal Adhesion Kinase (FAK) Over-Expression and Prognostic Implication in Pediatric Hepatocellular Carcinoma. Int. J. Mol. Sci. 2020, 21, 5795. [Google Scholar] [CrossRef] [PubMed]
- Wang, W.; Lollis, E.M.; Bordeleau, F.; Reinhart-King, C.A. Matrix stiffness regulates vascular integrity through focal adhesion kinase activity. FASEB J. 2019, 33, 1199–1208. [Google Scholar] [CrossRef]
- Chien, K.R.; Olson, E.N. Converging pathways and principles in heart development and disease: CV@CSH. Cell 2002, 110, 153–162. [Google Scholar] [CrossRef]
- Knoll, R.; Hoshijima, M.; Chien, K. Cardiac mechanotransduction and implications for heart disease. J. Mol. Med. 2003, 81, 750–756. [Google Scholar] [CrossRef] [PubMed]
- Franchini, K.G.; Torsoni, A.S.; Soares, P.H.; Saad, M.J. Early activation of the multicomponent signaling complex associated with focal adhesion kinase induced by pressure overload in the rat heart. Circ. Res. 2000, 87, 558–565. [Google Scholar] [CrossRef]
- Laser, M.; Willey, C.D.; Jiang, W.; Cooper, G.; Menick, D.R.; Zile, M.R.; Kuppuswamy, D. Integrin activation and focal complex formation in cardiac hypertrophy. J. Biol. Chem. 2000, 275, 35624–35630. [Google Scholar] [CrossRef]
- Furuta, Y.; Ilic, D.; Kanazawa, S.; Takeda, N.; Yamamoto, T.; Aizawa, S. Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK. Oncogene 1995, 11, 1989–1995. [Google Scholar]
- Peng, X.; Kraus, M.S.; Wei, H.; Shen, T.-L.; Pariaut, R.; Alcaraz, A.; Ji, G.; Cheng, L.; Yang, Q.; Kotlikoff, M.I.; et al. Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice. J. Clin. Invest. 2006, 116, 217–227. [Google Scholar] [CrossRef]
- Domingos, P.P.; Fonseca, P.M.; Nadruz, W., Jr.; Franchini, K.G. Load-induced focal adhesion kinase activation in the myocardium: Role of stretch and contractile activity. Am. J. Physiol. Heart Circ. Physiol. 2002, 282, H556–H564. [Google Scholar] [CrossRef]
- Yi, X.P.; Zhou, J.; Huber, L.; Qu, J.; Wang, X.; Gerdes, A.M.; Li, F. Nuclear compartmentalization of FAK and FRNK in cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 2006, 290, H2509–H2515. [Google Scholar] [CrossRef] [PubMed]
- Rosa, N.; Simoes, R.; Magalhaes, F.D.; Marques, A.T. From mechanical stimulus to bone formation: A review. Med. Eng. Phys. 2015, 37, 719–728. [Google Scholar] [CrossRef] [PubMed]
- Leucht, P.; Kim, J.B.; Currey, J.A.; Brunski, J.; Helms, J.A. FAK-Mediated mechanotransduction in skeletal regeneration. PLoS ONE 2007, 2, e390. [Google Scholar] [CrossRef] [PubMed]
- Rangaswami, H.; Schwappacher, R.; Tran, T.; Chan, G.C.; Zhuang, S.; Boss, G.R.; Pilz, R.B. Protein kinase G and focal adhesion kinase converge on Src/Akt/beta-catenin signaling module in osteoblast mechanotransduction. J. Biol. Chem. 2012, 287, 21509–21519. [Google Scholar] [CrossRef] [PubMed]
- Peruzzi, B.; Teti, A. The Physiology and Pathophysiology of the Osteoclast. Clin. Rev. Bone Miner. Metab. 2011, 10, 71–97. [Google Scholar] [CrossRef]
- Vaananen, H.K.; Zhao, H.; Mulari, M.; Halleen, J.M. The cell biology of osteoclast function. J. Cell Sci. 2000, 113 Pt 3, 377–381. [Google Scholar]
- Bi, H.; Chen, X.; Gao, S.; Yu, X.; Xiao, J.; Zhang, B.; Liu, X.; Dai, M. Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapies: A Review. Front. Med. 2017, 4, 234. [Google Scholar] [CrossRef]
- Xiao, Y.; Zijl, S.; Wang, L.; De Groot, D.C.; Van Tol, M.J.; Lankester, A.C.; Borst, J. Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis. Stem Cell Rep. 2015, 4, 984–994. [Google Scholar] [CrossRef]
- Ray, B.J.; Thomas, K.; Huang, C.S.; Gutknecht, M.F.; Botchwey, E.A.; Bouton, A.H. Regulation of osteoclast structure and function by FAK family kinases. J. Leukoc. Biol. 2012, 92, 1021–1028. [Google Scholar] [CrossRef]
- Bagi, C.M.; Roberts, G.W.; Andresen, C.J. Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: Implications for bone metastases. Cancer 2008, 112, 2313–2321. [Google Scholar] [CrossRef]
- Majeski, H.E.; Yang, J. The 2016 John, J. Abel Award Lecture: Targeting the Mechanical Microenvironment in Cancer. Mol. Pharmacol. 2016, 90, 744–754. [Google Scholar] [CrossRef] [PubMed]
- Schultze, A.; Fiedler, W. Therapeutic potential and limitations of new FAK inhibitors in the treatment of cancer. Expert Opin. Investig. Drugs 2010, 19, 777–788. [Google Scholar] [CrossRef] [PubMed]
- Lim, S.T.; Mikolon, D.; Stupack, D.G.; Schlaepfer, D.D. FERM control of FAK function: Implications for cancer therapy. Cell Cycle 2008, 7, 2306–2314. [Google Scholar] [CrossRef] [PubMed]
- Slack-Davis, J.K.; Martin, K.H.; Tilghman, R.W.; Iwanicki, M.; Ung, E.J.; Autry, C.; Luzzio, M.J.; Cooper, B.; Kath, J.C.; Roberts, W.G.; et al. Cellular characterization of a novel focal adhesion kinase inhibitor. J. Biol. Chem. 2007, 282, 14845–14852. [Google Scholar] [CrossRef]
- Roberts, W.G.; Ung, E.; Whalen, P.; Cooper, B.; Hulford, C.; Autry, C.; Richter, D.; Emerson, E.; Lin, J.; Kath, J.; et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res. 2008, 68, 1935–1944. [Google Scholar] [CrossRef]
- Stokes, J.B.; Adair, S.J.; Slack-Davis, J.K.; Walters, D.M.; Tilghman, R.W.; Hershey, E.D.; Lowrey, B.; Thomas, K.S.; Bouton, A.H.; Hwang, R.F.; et al. Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol. Cancer Ther. 2011, 10, 2135–2145. [Google Scholar] [CrossRef]
- Infante, J.R.; Camidge, D.R.; Mileshkin, L.R.; Chen, E.X.; Hicks, R.J.; Rischin, D.; Fingert, H.; Pierce, K.J.; Xu, H.; Roberts, W.G.; et al. Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors. J. Clin. Oncol. 2012, 30, 1527–1533. [Google Scholar] [CrossRef]
- Golubovskaya, V.M.; Virnig, C.; Cance, W.G. TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR. Mol. Carcinog. 2008, 47, 222–234. [Google Scholar] [CrossRef]
- Halder, J.; Lin, Y.G.; Merritt, W.M.; Spannuth, W.A.; Nick, A.M.; Honda, T.; Kamat, A.A.; Han, L.Y.; Kim, T.J.; Pluquet, O.; et al. Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res. 2007, 67, 10976–10983. [Google Scholar] [CrossRef]
- Shi, Q.; Hjelmeland, A.B.; Keir, S.T.; Song, L.; Wickman, S.; Jackson, D.; Ohmori, O.; Bigner, D.D.; Friedman, H.S.; Rich, J.N. A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth. Mol. Carcinog. 2007, 46, 488–496. [Google Scholar] [CrossRef]
- Jiang, H.; Hegde, S.; Knolhoff, B.L.; Zhu, Y.; Herndon, J.M.; Meyer, M.A.; Nywening, T.M.; Hawkins, T.M.N.W.G.; Shapiro, I.M.; Weaver, D.T.; et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 2016, 22, 851–860. [Google Scholar] [CrossRef] [PubMed]
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Urciuoli, E.; Peruzzi, B. Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction. Int. J. Mol. Sci. 2020, 21, 9426. https://doi.org/10.3390/ijms21249426
Urciuoli E, Peruzzi B. Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction. International Journal of Molecular Sciences. 2020; 21(24):9426. https://doi.org/10.3390/ijms21249426
Chicago/Turabian StyleUrciuoli, Enrica, and Barbara Peruzzi. 2020. "Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction" International Journal of Molecular Sciences 21, no. 24: 9426. https://doi.org/10.3390/ijms21249426
APA StyleUrciuoli, E., & Peruzzi, B. (2020). Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction. International Journal of Molecular Sciences, 21(24), 9426. https://doi.org/10.3390/ijms21249426