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Endothelial Cell Signaling During Wound Healing
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
The activation of FAK may support focal adhesion formation by phosphorylating other cytoskeletal proteins directly. One candidate is the vinculin-binding protein paxillin,85 which is tyrosine phosphorylated during integrin-mediated cell adhesion.68,69 FAK and paxillin colocalize in focal adhesions and have similar tyrosine phosphorylation patterns during development and neuropeptide stimulation.107,108 The phosphotyrosine content of paxillin also correlates with FAK expression in cells that overexpress the focal adhesion kinase.87 This correlation has also been observed for tensin,87 another focal adhesion protein that is tyrosine phosphorylated during integrin-mediated cell-ECM adhesion.109 Tensin is known to contain an SH2 domain,110 and this may facilitate a binding interaction with paxillin or FAK. Finally, a 130-kDa nonkinase phosphoprotein has been described in fibroblasts that is tyrosine phosphorylated during integrin-mediated cell adhesion,111 and may represent another FAK substrate.
Liposomes in the Delivery Of Antisense Oligonucleotides
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
Therapeutic studies of antisense sequence to focal adhesion kinase in human tumor lines in nude mice are under investigation (Huang et al., 1996). When 150 mM lipid and 100 mg/mL oligonucleotide solution were used, 10% of molecules were encapsulated. Different sterically stabilized liposomes were tried in order to encapsulate or bind to a partially cationic surface. Targeted liposomes containing Fab’ fragments attached to the far end of the PEG chain were also used. Physicochemical characteristics of complexes and their biological stability and interactability were also followed (Meyer et al. 1996).
Structure, Biochemical Properties, and Biological Functions of Integrin Cytoplasmic Domains
Published in Yoshikazu Takada, Integrins: The Biological Problems, 2017
Martin E. Hemler, Jonathan B. Weitzman, Renata Pasqualini, Satoshi Kawaguchi, Paul D. Kassner, Feodor B. Berdichevsky
When the integrin family of adhesion receptors was first described,1–4 initial emphasis focused on identifying α and β subunits, and on elucidating the ligand-binding specificities for the various heterodimers. More recently, there has been a major focus on signaling through integrins, and several reviews have been written, concentrating on general aspects,5 specific pathways,6 extracellular matrix involvement,7 regulation of lymphocyte adhesion,8 and the involvement of focal adhesion kinase (FAK).9
2-Arylquinolines as novel anticancer agents with dual EGFR/FAK kinase inhibitory activity: synthesis, biological evaluation, and molecular modelling insights
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mostafa M. Elbadawi, Wagdy M. Eldehna, Amer Ali Abd El-Hafeez, Warda R. Somaa, Amgad Albohy, Sara T. Al-Rashood, Keli K. Agama, Eslam B. Elkaeed, Pradipta Ghosh, Yves Pommier, Manabu Abe
Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase involved in signal transductions from cell adhesions to regulate different biological cell functions including survival and cell migration13,14. Also, it is activated and overexpressed in diverse cancer types controlling cancer proliferation, survival and metastasis. Thus, FAK has been identified as a promising druggable target for targeted cancer therapy. Currently, several FAK inhibitors, such as 2,4-diaminopyridine derivative GSK2256098 and 2,4-diaminopyrimidine derivative Defactinib (Figure 1), are currently being evaluated in clinical trials for cancer treatment, in addition to the 2,4-diaminopyrimidine derivative TAE-226 (Figure 1) which displayed potent antitumor impact in different cancer types in vivo and in vitro and usually used as a reference drug7,15,16. Noteworthy, it was established that the most affected colorectal cancer expressed high levels of EGFR and FAK that particularly correlated with tumour angiogenesis, cancer aggressiveness and poor prognosis17,18.
Improved anticancer activity of betulinic acid on breast cancer through a grafted copolymer-based micelles system
Published in Drug Delivery, 2021
Xueju Qi, Cong Gao, Chuanjin Yin, Junting Fan, Xiaochen Wu, Chuanlong Guo
Tumor growth depends on angiogenesis and is affected by multiple signaling pathways. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a basic role in signal transduction mediated by integrins and growth factors, and plays a vital role in cell migration and proliferation (Tavora et al. 2010; Chen et al. 2012). Moreover, tumor cells can release growth factors (e.g., VEGF) into the microenvironment, thereby activating the proliferation of vascular endothelial cells and inducing tumor metastasis (Pang et al. 2011; Bi et al. 2017). Recently, it was discovered that Hypoxia inducible factor-1 (HIF-1) directly regulates the expression of VEGF at the gene level and is an important regulator of malignant tumor-induced angiogenesis (Palazon et al. 2017). In this study, the expression of HIF-1 and VEGF was restrained by free BA as well as Soluplus-BA micelles, while Soluplus-BA micelles showed a more significant inhibitory effect. In addition, BA decreased FAK phosphorylation in HUVEC cells (Figure 7(C)). The angiogenesis inhibitory effect of BA may be accomplished by regulating the HIF-1/VEGF-FAK signaling pathway.
The role of CMV in glioblastoma and implications for immunotherapeutic strategies
Published in OncoImmunology, 2019
Maryam Rahman, Farhad Dastmalchi, Aida Karachi, Duane Mitchell
Beyond identification of CMV within glioma samples, several studies have investigated the effect of CMV infection in glioma pathogenesis. By infecting human glioma tumor cells with CMV, investigators discovered activation of the phosphatidylinositol-3-kinase (PI3K)-Akt pathway.24 They also found phosphorylation of focal adhesion kinase (FAK) resulting in increased tumor cell migration and invasiveness. This group also described that expression of IE1 CMV genes in human GBM cell lines resulted in increased entry into the cell cycle, DNA synthesis and cellular proliferation.25 Overexpression of CMV glycoprotein B in glioma cells also induced entry into the cell cycle and increased invasiveness.26 However, this effect was mediated through phosphorylation of PDGFRα which had been previously shown to be a critical receptor for CMV infection.27 Straat et al. infected malignant glioma cell lines with CMV and found that this resulted in activated telomerase in tumor cells.28 They hypothesized that this effect could be a link between viral infection and oncogenesis.