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Search Results (4)
  • Open Access

    ARTICLE

    Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

    XINFENG ZHANG1,2,#, SHUANG LI2,#, MEIRU SONG1,2, YUE CHEN3, LIANGZHENG CHANG3, ZHERUI LIU4, HONGYUAN DAI3, YUTAO WANG4, GANGQI YANG3, YUN JIANG5,6,*, YINYING LU1,2,*

    Oncology Research, Vol.32, No.4, pp. 679-690, 2024, DOI:10.32604/or.2024.046231

    Abstract Liver cancer is a prevalent malignant cancer, ranking third in terms of mortality rate. Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer. Hepatocellular carcinoma (HCC) has low expression of focal adhesion kinase (FAK), which increases the risk of metastasis and recurrence. Nevertheless, the efficacy of FAK phosphorylation inhibitors is currently limited. Thus, investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis. This study examined the correlation between FAK expression and the prognosis of HCC. Additionally, we explored the impact of… More >

  • Open Access

    ARTICLE

    Inhibition of focal adhesion kinase by antisense oligonucleotides enhances the sensitivity of breast cancer cells to camptothecins

    T.H. Satoh2, T.A. Surmacz3, O. Nyormoi4, C.M. Whitacre1

    BIOCELL, Vol.27, No.1, pp. 47-55, 2003, DOI:10.32604/biocell.2003.27.047

    Abstract This study shows a strong association between cell attachment to substratum and activation of β1-integrin-signaling with resistance to the camptothecin derivative topotecan (TPT) in breast cancer cells. We propose a mechanistic-driven approach to sensitize the cells to camptothecins. ZR-75-1 anchoragedependent breast cancer cell line, its derivative 9D3S suspension cells (9D3S-S), and 9D3S cells attached to fibronectin-coated plates (9D3S-A) were treated with TPT (1 µM) or CPT-11 (40 µM) for 48 h. Programmed cell death (PCD), as shown by poly(ADP-ribose) polymerase (PARP), pro-caspase-3 and pro-caspase-9 cleavage, was observed in 9D3S-S cells but not in ZR-75-1 or 9D3S-A cells. Because p125 focal… More >

  • Open Access

    ARTICLE

    Focal Adhesion Kinase Signaling Controls Cyclic Tensile Strain Enhanced Collagen I-Induced Osteogenic Differentiation of Human Mesenchymal Stem Cells

    Donald F. Ward Jr.*, William A. Williams*, Nicole E. Schapiro*, Samuel R. Christy*, Genevieve L. Weber*, Megan Salt, Robert F. Klees*, Adele Boskey, George E. Plopper ∗,‡

    Molecular & Cellular Biomechanics, Vol.4, No.4, pp. 177-188, 2007, DOI:10.3970/mcb.2007.004.177

    Abstract Focal adhesion kinase (FAK) is a key integrator of integrin-mediated signals from the extracellular matrix to the cytoskeleton and downstream signaling molecules. FAK is activated by phosphorylation at specific tyrosine residues, which then stimulate downstream signaling including the ERK1/2 pathway, leading to a variety of cellular responses. In this study, we examined the effects of FAK point mutations at tyrosine residues (Y397, Y925, Y861, and Y576/7) on osteogenic differentiation of human mesenchymal stem cells exposed to collagen I and cyclic tensile strain. Our results demonstrate that FAK signaling emanating from Y397, Y925, and to a lesser extent Y576/7, but not… More >

  • Open Access

    ARTICLE

    Substrate Modulation of Osteoblast Adhesion Strength, Focal Adhesion Kinase Activation, and Responsiveness to Mechanical Stimuli

    E. Takai1, R. Landesberg2, R.W. Katz2, C.T. Hung3, X.E Guo1,4

    Molecular & Cellular Biomechanics, Vol.3, No.1, pp. 1-12, 2006, DOI:10.3970/mcb.2006.003.001

    Abstract Osteoblast interactions with extracellular matrix (ECM) proteins are known to influence many cell functions, which may ultimately affect osseointegration of implants with the host bone tissue. Some adhesion-mediated events include activation of focal adhesion kinase, and subsequent changes in the cytoskeleton and cell morphology, which may lead to changes in adhesion strength and cell responsiveness to mechanical stimuli. In this study we examined focal adhesion kinase activation (FAK), F-actin cytoskeleton reorganization, adhesion strength, and osteoblast responsiveness to fluid shear when adhered to type I collagen (ColI), glass, poly-L-lysine (PLL), fibronectin (FN), vitronectin (VN), and serum (FBS). In general, surfaces that… More >

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