Now showing items 1-11 of 11

    • Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration. 

      Croft, DR; Coleman, ML; Li, S; Robertson, D; Sullivan, T; Stewart, CL; Olson, MF (2005-01-17)
      Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and ...
    • Assessing histone demethylase inhibitors in cells: lessons learned. 

      Hatch, SB; Yapp, C; Montenegro, RC; Savitsky, P; Gamble, V; Tumber, A; Ruda, GF; Bavetsias, V; Fedorov, O; Atrash, B; Raynaud, F; Lanigan, R; Carmichael, L; Tomlin, K; Burke, R; Westaway, SM; Brown, JA; Prinjha, RK; Martinez, ED; Oppermann, U; Schofield, CJ; Bountra, C; Kawamura, A; Blagg, J; Brennan, PE; Rossanese, O; Müller, S (2017)
      BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ...
    • Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells. 

      Rodgers, UR; Lanyon-Hogg, T; Masumoto, N; Ritzefeld, M; Burke, R; Blagg, J; Magee, AI; Tate, EW (2016-12-16)
      The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ...
    • DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. 

      Mateo, J; Carreira, S; Sandhu, S; Miranda, S; Mossop, H; Perez-Lopez, R; Nava Rodrigues, D; Robinson, D; Omlin, A; Tunariu, N; Boysen, G; Porta, N; Flohr, P; Gillman, A; Figueiredo, I; Paulding, C; Seed, G; Jain, S; Ralph, C; Protheroe, A; Hussain, S; Jones, R; Elliott, T; McGovern, U; Bianchini, D; Goodall, J; Zafeiriou, Z; Williamson, CT; Ferraldeschi, R; Riisnaes, R; Ebbs, B; Fowler, G; Roda, D; Yuan, W; Wu, YM; Cao, X; Brough, R; Pemberton, H; A'Hern, R; Swain, A; Kunju, LP; Eeles, R; Attard, G; Lord, CJ; Ashworth, A; Rubin, MA; Knudsen, KE; Feng, FY; Chinnaiyan, AM; Hall, E; de Bono, JS
      Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to ...
    • Inhibiting the phosphoinositide 3-kinase pathway for cancer treatment. 

      Workman, P (2004-04)
      There is extensive evidence from the molecular and genomic analysis of human cancers that the PI 3-kinase (phosphoinositide 3-kinase)-Akt/PKB (protein kinase B) pathway is deregulated in malignant progression. Furthermore, ...
    • Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. 

      Tang, H; Leung, L; Saturno, G; Viros, A; Smith, D; Di Leva, G; Morrison, E; Niculescu-Duvaz, D; Lopes, F; Johnson, L; Dhomen, N; Springer, C; Marais, R (2017-04-18)
      Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor ...
    • Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. 

      Chan, F; Sun, C; Perumal, M; Nguyen, QD; Bavetsias, V; McDonald, E; Martins, V; Wilsher, NE; Raynaud, FI; Valenti, M; Eccles, S; Te Poele, R; Workman, P; Aboagye, EO; Linardopoulos, S (2007-12)
      The Aurora family of serine/threonine kinases is important for the regulation of centrosome maturation, chromosome segregation, and cytokinesis during mitosis. Overexpression of Aurora kinases in mammalian cells leads to ...
    • Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. 

      Wan, PT; Garnett, MJ; Roe, SM; Lee, S; Niculescu-Duvaz, D; Good, VM; Jones, CM; Marshall, CJ; Springer, CJ; Barford, D; Marais, R (2004-03)
      Over 30 mutations of the B-RAF gene associated with human cancers have been identified, the majority of which are located within the kinase domain. Here we show that of 22 B-RAF mutants analyzed, 18 have elevated kinase ...
    • Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

      Mariotti, L; Pollock, K; Guettler, S (2017-12)
      The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
    • Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

      Mariotti, L; Pollock, K; Guettler, S (2017-12)
      The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
    • Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. 

      Chapman, PB; Robert, C; Larkin, J; Haanen, JB; Ribas, A; Hogg, D; Hamid, O; Ascierto, PA; Testori, A; Lorigan, PC; Dummer, R; Sosman, JA; Flaherty, KT; Chang, I; Coleman, S; Caro, I; Hauschild, A; McArthur, GA (2017-10-01)
      Background: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAFV600 mutation-positive metastatic melanoma. ...