FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis

被引:126
作者
Lachowski, Dariusz [1 ]
Cortes, Ernesto [1 ]
Robinson, Benjamin [1 ]
Rice, Alistair [1 ]
Rombouts, Krista [2 ]
Hernandez, Armando E. Del Rio [1 ]
机构
[1] Imperial Coll London, Dept Bioengn, Cellular & Mol Biomech Lab, London SW7 2AZ, England
[2] UCL, Inst Liver & Digest Hlth, Royal Free Hosp, Regenerat Med & Fibrosis Grp, London NW3 2PF, England
基金
欧洲研究理事会;
关键词
mechanotransduction; focal adhesions; directed migration; FOCAL ADHESION KINASE; MATRIX STIFFNESS; PATHWAY; YAP/TAZ; CELLS; MECHANOTRANSDUCERS; HOMEOSTASIS; CARCINOMA; RIGIDITY; SIZE;
D O I
10.1096/fj.201700721R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes in cells such as growth, survival, and migration. FAK is one of the first molecules recruited to focal adhesions in response to external mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling, and relays these stimuli to other mechanotransducers within the cytoplasm. Yes-associated protein (YAP) has been identified recently as one of these core mechanotransducers. YAP translocates to the nucleus following changes in cell mechanics to promote the expression of genes implicated in motility, apoptosis, proliferation, and organ growth. Here, we show that FAK controls the nuclear translocation and activation of YAP in response to mechanical activation and submit that the YAP-dependent process of durotaxis requires a cell with an asymmetric distribution of active and inactive FAK molecules.
引用
收藏
页码:1099 / 1107
页数:9
相关论文
共 41 条
  • [1] Adhesive ligand tether length affects the size and length of focal adhesions and influences cell spreading and attachment
    Attwood, Simon J.
    Cortes, Ernesto
    Haining, Alexander William M.
    Robinson, Benjamin
    Li, Danyang
    Gautrot, Julien
    Hernandez, Armando del Rio
    [J]. SCIENTIFIC REPORTS, 2016, 6
  • [2] Hepatic stellate cells and extracellular matrix in hepatocellular carcinoma: more complicated than ever
    Carloni, Vinicio
    Tu Vinh Luong
    Rombouts, Krista
    [J]. LIVER INTERNATIONAL, 2014, 34 (06) : 834 - 843
  • [3] Agrin as a Mechanotransduction Signal Regulating YAP through the Hippo Pathway
    Chakraborty, Sayan
    Njah, Kizito
    Pobbati, Ajaybabu V.
    Lim, Ying Bena
    Raju, Anandhkumar
    Lakshmanan, Manikandan
    Tergaonkar, Vinay
    Lim, Chwee Teck
    Hong, Wanjin
    [J]. CELL REPORTS, 2017, 18 (10): : 2464 - 2479
  • [4] Role of YAP/TAZ in mechanotransduction
    Dupont, Sirio
    Morsut, Leonardo
    Aragona, Mariaceleste
    Enzo, Elena
    Giulitti, Stefano
    Cordenonsi, Michelangelo
    Zanconato, Francesca
    Le Digabel, Jimmy
    Forcato, Mattia
    Bicciato, Silvio
    Elvassore, Nicola
    Piccolo, Stefano
    [J]. NATURE, 2011, 474 (7350) : 179 - U212
  • [5] Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury
    Friedman, SL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) : 2247 - 2250
  • [6] Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells
    Gaggioli, Cedric
    Hooper, Steven
    Hidalgo-Carcedo, Cristina
    Grosse, Robert
    Marshall, John F.
    Harrington, Kevin
    Sahai, Erik
    [J]. NATURE CELL BIOLOGY, 2007, 9 (12) : 1392 - U92
  • [7] A Small Molecule Inhibitor, 1,2,4,5-Benzenetetraamine Tetrahydrochloride, Targeting the Y397 Site of Focal Adhesion Kinase Decreases Tumor Growth
    Golubovskaya, Vita M.
    Nyberg, Carl
    Zheng, Min
    Kweh, Frederick
    Magis, Andrew
    Ostrov, David
    Cance, William G.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (23) : 7405 - 7416
  • [8] Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression
    Handorf, Andrew M.
    Zhou, Yaxian
    Halanski, Matthew A.
    Li, Wan-Ju
    [J]. ORGANOGENESIS, 2015, 11 (01) : 1 - 15
  • [9] Experimental validation of atomic force microscopy-based cell elasticity measurements
    Harris, Andrew R.
    Charras, G. T.
    [J]. NANOTECHNOLOGY, 2011, 22 (34)
  • [10] The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment
    Johnson, Randy
    Halder, Georg
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2014, 13 (01) : 63 - 79