A novel small-molecule MRCK inhibitor blocks cancer cell invasion

Cell Communication and Signaling

Volumn 12, Issue 1, 2014, Pages

  Unbekandt, Mathieu ^a   Croft, Daniel R ^a   Crighton, Diane ^a   Mezna, Mokdad ^a   McArthur, Duncan ^a   McConnell, Patricia ^a   Schüttelkopf, Alexander W ^a   Belshaw, Simone ^a   Pannifer, Andrew ^a,b   Sime, Mairi ^a   Bower, Justin ^a   Drysdale, Martin ^a   Olson, Michael F ^a  

^a BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

^b European Screening Centre   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 CHLORO 1 (4 PIPERIDYL) N [5 (2 PYRIDYL) 1H PYRAZOL 4 YL]PYRAZOLE 3 CARBOXAMIDE; ANTINEOPLASTIC AGENT; MYOSIN LIGHT CHAIN 2; MYOTONIC DYSTROPHY CDC42 BINDING KINASE BETA; MYOTONIC DYSTROPHY CDC42 BINDING KINASE INHIBITOR; MYOTONIC DYSTROPHY PROTEIN KINASE; PROTEIN CDC42; PROTEIN ROCK1; PROTEIN ROCK2; RHO KINASE; UNCLASSIFIED DRUG; 4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; 4-CHLORO-1-(4-PIPERIDYL)-N-(5-(2-PYRIDYL)-1H-PYRAZOL-4-YL)PYRAZOLE-3-CARBOXAMIDE; AMIDE; CDC42BPA PROTEIN, HUMAN; CDC42BPB PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; ROCK1 PROTEIN, HUMAN; ROCK2 PROTEIN, HUMAN;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; BINDING SITE; CANCER CELL; CELL MOTILITY; CONCENTRATION RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; LIGAND BINDING; PHARMACOLOGICAL BLOCKING; PROTEIN PHOSPHORYLATION; SQUAMOUS CELL CARCINOMA; STRUCTURE ACTIVITY RELATION; TUMOR INVASION; ANTAGONISTS AND INHIBITORS; CELL MOTION; DRUG EFFECTS; METABOLISM; TUMOR CELL LINE;

AMIDES; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL MOVEMENT; HUMANS; MYOTONIN-PROTEIN KINASE; NEOPLASM INVASIVENESS; PROTEIN KINASE INHIBITORS; PYRAZOLES; PYRIDINES; RHO-ASSOCIATED KINASES;

EID: 84907969229     PISSN: None     EISSN: 1478811X     Source Type: Journal    
DOI: 10.1186/s12964-014-0054-x     Document Type: Article

References (43)

1. Hallmarks of cancer: the next generation. D Hanahan, A Weinberg Robert, Cell 2011 144 646 674 10.1016/j.cell.2011.02.013 21376230
2. The actin cytoskeleton in cancer cell motility. MF Olson, E Sahai, Clin Exp Metastasis 2009 26 273 287 10.1007/s10585-008-9174-2 18498004
3. Non-muscle myosin II takes centre stage in cell adhesion and migration. M Vicente-Manzanares, X Ma, RS Adelstein, AR Horwitz, Nat Rev Mol Cell Biol 2009 10 778 790 10.1038/nrm2786 19851336
4. The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer. M Unbekandt, MF Olson, J Mol Med (Berl) 2014 92 217 225 10.1007/s00109-014-1133-6
5. The nuts and bolts of AGC protein kinases. LR Pearce, D Komander, DR Alessi, Nat Rev Mol Cell Biol 2010 11 9 22 10.1038/nrm2822 20027184
6. Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion. S Wilkinson, HF Paterson, CJ Marshall, Nat Cell Biol 2005 7 255 261 10.1038/ncb1230 15723050
7. Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta. SH Choi, G Czifra, N Kedei, NE Lewin, J Lazar, Y Pu, VE Marquez, PM Blumberg, J Biol Chem 2008 283 10543 10549 10.1074/jbc.M707463200 18263588
8. Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization. T Leung, X-QQ Chen, I Tan, E Manser, L Lim, Mol Cell Biol 1998 18 130 140 9418861
9. A tripartite complex containing MRCK modulates lamellar actomyosin retrograde flow. I Tan, J Yong, JM Dong, L Lim, T Leung, Cell 2008 135 123 136 10.1016/j.cell.2008.09.018 18854160
10. Distinct roles of MLCK and ROCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration of fibroblasts. G Totsukawa, Y Wu, Y Sasaki, DJ Hartshorne, Y Yamakita, S Yamashiro, F Matsumura, J Cell Biol 2004 164 427 439 10.1083/jcb.200306172 14757754
11. Co-crystal structures of inhibitors with MRCKbeta, a key regulator of tumor cell invasion. T Heikkila, E Wheatley, D Crighton, E Schroder, A Boakes, SJ Kaye, M Mezna, L Pang, M Rushbrooke, A Turnbull, MF Olson, PLoS One 2011 6 24825 10.1371/journal.pone.0024825 21949762
12. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. C Gaggioli, S Hooper, C Hidalgo-Carcedo, R Grosse, JF Marshall, K Harrington, E Sahai, Nat Cell Biol 2007 9 1392 1400 10.1038/ncb1658 18037882
13. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCK-alpha kinases. K Lefort, A Mandinova, P Ostano, V Kolev, V Calpini, I Kolfschoten, V Devgan, J Lieb, W Raffoul, D Hohl, V Neel, J Garlick, G Chiorino, GP Dotto, Genes Dev 2007 21 562 577 10.1101/gad.1484707 17344417
14. Gene expression profiling predicts clinical outcome of breast cancer. LJ van 't Veer, H Dai, MJ van de Vijver, YD He, AAM Hart, M Mao, HL Peterse, K van der Kooy, MJ Marton, AT Witteveen, GJ Schreiber, RM Kerkhoven, C Roberts, PS Linsley, R Bernards, SH Friend, Nature 2002 415 530 536 10.1038/415530a 11823860
15. The role of ligand efficiency metrics in drug discovery. AL Hopkins, GM Keseru, PD Leeson, DC Rees, CH Reynolds, Nat Rev Drug Discov 2014 13 105 121 10.1038/nrd4163 24481311
16. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. C Yung-Chi, WH Prusoff, Biochem Pharmacol 1973 22 3099 3108 10.1016/0006-2952(73)90196-2
17. The protein kinase complement of the human genome. G Manning, DB Whyte, R Martinez, T Hunter, S Sudarsanam, Science 2002 298 1912 1934 10.1126/science.1075762 12471243
18. Kinome Render: a stand-alone and web-accessible tool to annotate the human protein kinome tree. M Chartier, T Chenard, J Barker, R Najmanovich, Peer J 2013 1 126 10.7717/peerj.126 23940838
19. The structure of dimeric ROCK I reveals the mechanism for ligand selectivity. M Jacobs, K Hayakawa, L Swenson, S Bellon, M Fleming, P Taslimi, J Doran, J Biol Chem 2006 281 260 268 10.1074/jbc.M508847200 16249185
20. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. M Uehata, T Ishizaki, H Satoh, T Ono, T Kawahara, T Morishita, H Tamakawa, K Yamagami, J Inui, M Maekawa, S Narumiya, Nature 1997 389 990 994 10.1038/40187 9353125
21. Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization. K Ando, S Fukuhara, T Moriya, Y Obara, N Nakahata, N Mochizuki, J Cell Biol 2013 202 901 916 10.1083/jcb.201301115 24019534
22. Cdc42-dependent formation of the ZO-1/MRCKbeta complex at the leading edge controls cell migration. L Huo, W Wen, R Wang, C Kam, J Xia, W Feng, M Zhang, EMBO J 2011 30 665 678 10.1038/emboj.2010.353 21240187
23. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. J O'Brien, I Wilson, T Orton, F Pognan, Eur J Biochem 2000 267 5421 5426 10.1046/j.1432-1327.2000.01606.x 10951200
24. PDK1-mediated activation of MRCKalpha regulates directional cell migration and lamellipodia retraction. PA Gagliardi, L di Blasio, A Puliafito, G Seano, R Sessa, F Chianale, T Leung, F Bussolino, L Primo, J Cell Biol 2014 206 415 434 10.1083/jcb.201312090 25092657
25. MT1-MMP- and Cdc42-dependent signaling co-regulate cell invasion and tunnel formation in 3D collagen matrices. KE Fisher, A Sacharidou, AN Stratman, AM Mayo, SB Fisher, RD Mahan, MJ Davis, GE Davis, J Cell Sci 2009 122 4558 4569 10.1242/jcs.050724 19934222
26. ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. B Rafn, CF Nielsen, SH Andersen, P Szyniarowski, E Corcelle-Termeau, E Valo, N Fehrenbacher, CJ Olsen, M Daugaard, C Egebjerg, T Bottzauw, P Kohonen, J Nylandsted, S Hautaniemi, J Moreira, M Jaattela, T Kallunki, Mol Cell 2012 45 764 776 10.1016/j.molcel.2012.01.029 22464443
27. Ser1333 phosphorylation indicates ROCKI activation. HH Chuang, SW Liang, ZF Chang, HH Lee, J Biomed Sci 2013 20 83 10.1186/1423-0127-20-83 24168723
28. ROCKII Ser1366 phosphorylation reflects the activation status. HH Chuang, CH Yang, YG Tsay, CY Hsu, LM Tseng, ZF Chang, HH Lee, Biochem J 2012 443 145 151 10.1042/BJ20111839 22273145
29. Chelerythrine is a potent and specific inhibitor of protein kinase C. JM Herbert, JM Augereau, J Gleye, JP Maffrand, Biochem Biophys Res Commun 1990 172 993 999 10.1016/0006-291X(90)91544-3 2244923
30. Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase. I Tan, J Lai, J Yong, SF Li, T Leung, FEBS Lett 2011 585 1260 1268 10.1016/j.febslet.2011.03.054 21457715
31. Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine. G Brunhofer, A Fallarero, D Karlsson, A Batista-Gonzalez, P Shinde, C Gopi Mohan, P Vuorela, Bioorg Med Chem 2012 20 6669 6679 10.1016/j.bmc.2012.09.040 23062825
32. Chelerythrine rapidly induces apoptosis through generation of reactive oxygen species in cardiac myocytes. S Yamamoto, K Seta, C Morisco, SF Vatner, J Sadoshima, J Mol Cell Cardiol 2001 33 1829 1848 10.1006/jmcc.2001.1446 11603925
33. The benzophenanthridine alkaloid chelerythrine binds to DNA by intercalation: Photophysical aspects and thermodynamic results of iminium versus alkanolamine interaction. P Basu, D Bhowmik, G Suresh Kumar, J Photochem Photobiol B 2013 129 57 68 10.1016/j.jphotobiol.2013.09.011 24177205
34. Xds. W Kabsch, Acta Crystallogr D Biol Crystallogr 2010 66 125 132 10.1107/S0907444909047337 20124692
35. Molecular replacement with MOLREP. A Vagin, A Teplyakov, Acta Crystallogr D Biol Crystallogr 2010 66 22 25 10.1107/S0907444909042589 20057045
36. Features and development of Coot. P Emsley, B Lohkamp, WG Scott, K Cowtan, Acta Crystallogr D Biol Crystallogr 2010 66 486 501 10.1107/S0907444910007493 20383002
37. PHENIX: a comprehensive Python-based system for macromolecular structure solution. PD Adams, PV Afonine, G Bunkoczi, VB Chen, IW Davis, N Echols, JJ Headd, LW Hung, GJ Kapral, RW Grosse-Kunstleve, AJ McCoy, NW Moriarty, R Oeffner, RJ Read, DC Richardson, JS Richardson, TC Terwilliger, PH Zwart, Acta Crystallogr D Biol Crystallogr 2010 66 213 221 10.1107/S0907444909052925 20124702
38. Refinement of macromolecular structures by the maximum-likelihood method. GN Murshudov, AA Vagin, EJ Dodson, Acta Crystallogr D Biol Crystallogr 1997 53 240 255 10.1107/S0907444996012255 15299926
39. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. AW Schuttelkopf, DM van Aalten, Acta Crystallogr D Biol Crystallogr 2004 60 1355 1363 10.1107/S0907444904011679 15272157
40. PROCHECK: a program to check the stereochemical quality of protein structures. RA Laskowski, MW MacArthur, DS Moss, JM Thornton, J App Crystall 1993 26 283 291 10.1107/S0021889892009944
41. The Rho GTPase effector ROCK regulates Cyclin A, Cyclin D1, and p27Kip1 levels by distinct mechanisms. DR Croft, MF Olson, Mol Cell Biol 2006 26 4612 4627 10.1128/MCB.02061-05 16738326
42. Localization of myotonic dystrophy protein kinase in human and rabbit tissues using a new panel of monoclonal antibodies. YC Pham, N Man, LT Lam, GE Morris, Hum Mol Genet 1998 7 1957 1965 10.1093/hmg/7.12.1957 9811941
43. Characterization of a monoclonal antibody panel shows that the myotonic dystrophy protein kinase, DMPK, is expressed almost exclusively in muscle and heart. LT Lam, YC Pham, TM Nguyen, GE Morris, Hum Mol Genet 2000 9 2167 2173 10.1093/hmg/9.14.2167 10958655