Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes

Cancer Cell

Volumn 28, Issue 2, 2015, Pages 170-182

  Herrero, Ana ^a   Pinto, Adán ^a   Colón Bolea, Paula ^a   Casar, Berta ^a   Jones, Mary ^b   Agudo Ibáñez, Lorena ^a   Vidal, Rebeca ^a,c   Tenbaum, Stephan P ^d   Nuciforo, Paolo ^d   Valdizán, Elsa M ^a,c   Horvath, Zoltan ^e   Orfi, Laszlo ^e,f   Pineda Lucena, Antonio ^g   Bony, Emilie ^h   Keri, Gyorgy ^e,f   Rivas, Germán ⁱ   Pazos, Angel ^a,c   Gozalbes, Rafael ^j   Palmer, Héctor G ^d   Hurlstone, Adam ^c   Crespo, Piero ^a   more..

^a UNIVERSITY OF CANTABRIA   (Spain)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE SALUD MENTAL CIBERSAM   (Spain)

^d VALL D HEBRON UNIVERSITY HOSPITAL   (Spain)

^e Vichem Chemie Research Ltd   (Hungary)

^f SEMMELWEIS UNIVERSITY   (Hungary)

^g CENTRO DE INVESTIGACIÓN PRÍNCIPE FELIPE   (Spain)

^h UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

ⁱ CENTRO DE INVESTIGACIONES BIOLÓGICAS   (Spain)

^j ProtoQSAR SL   (Spain)

more..

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; ANTINEOPLASTIC AGENT; DEL 22379; DIMER; INDOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MONOMER; RAS PROTEIN; REGULATOR PROTEIN; UNCLASSIFIED DRUG; DEL-22379; MAPK1 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE 1; MOLECULAR LIBRARY; PROTEIN BINDING; PROTEIN KINASE INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CARCINOGENESIS; CATALYSIS; COLORECTAL CANCER; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOSTASIS; DIMERIZATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FEMALE; HCT116 CELL LINE; HEK293 CELL LINE; HELA CELL LINE; HUMAN; HUMAN CELL; IC50; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; METASTASIS INHIBITION; MOUSE; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; CHICK EMBRYO; DRUG EFFECTS; DRUG SCREENING; IMMUNOBLOTTING; METABOLISM; MOLECULAR LIBRARY; NONOBESE DIABETIC MOUSE; NUDE MOUSE; PHARMACOLOGY; PROCEDURES; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE; SCID MOUSE; TUMOR CELL LINE; ZEBRA FISH;

ANIMALS; CARCINOGENESIS; CELL LINE, TUMOR; CELL PROLIFERATION; CHICK EMBRYO; FEMALE; HEK293 CELLS; HUMANS; IMMUNOBLOTTING; INDOLES; MICE, INBRED C57BL; MICE, INBRED NOD; MICE, NUDE; MICE, SCID; MITOGEN-ACTIVATED PROTEIN KINASE 1; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; RAS PROTEINS; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES; XENOGRAFT MODEL ANTITUMOR ASSAYS; ZEBRAFISH;

EID: 84939424868     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2015.07.001     Document Type: Article

References (36)

1. Arozarena I., Calvo F., Crespo P. Ras, an actor on many stages: posttranslational modifications, localization, and site-specified events. Genes Cancer 2011, 2:182-194.
2. Bollag G., Hirth P., Tsai J., Zhang J., Ibrahim P.N., Cho H., Spevak W., Zhang C., Zhang Y., Habets G., et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010, 467:596-599.
3. Calvo F., Agudo-Ibáñez L., Crespo P. The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumor therapies. BioEssays 2010, 32:412-421.
4. Canagarajah B.J., Khokhlatchev A., Cobb M.H., Goldsmith E.J. Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. Cell 1997, 90:859-869.
5. Casar B., Pinto A., Crespo P. Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes. Mol. Cell 2008, 31:708-721.
6. Casar B., Pinto A., Crespo P. ERK dimers and scaffold proteins: unexpected partners for a forgotten (cytoplasmic) task. Cell Cycle 2009, 8:1007-1013.
7. Deryugina E.I., Quigley J.P. Chick embryo chorioallantoic membrane model systems to study and visualize human tumor cell metastasis. Histochem. Cell Biol. 2008, 130:1119-1130.
8. Emery C.M., Vijayendran K.G., Zipser M.C., Sawyer A.M., Niu L., Kim J.J., Hatton C., Chopra R., Oberholzer P.A., Karpova M.B., et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc. Natl. Acad. Sci. USA 2009, 106:20411-20416.
9. Formstecher E., Ramos J.W., Fauquet M., Calderwood D.A., Hsieh J.C., Canton B., Nguyen X.T., Barnier J.V., Camonis J., Ginsberg M.H., Chneiweiss H. PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase. Dev. Cell 2001, 1:239-250.
10. Freeman A.K., Ritt D.A., Morrison D.K. Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling. Mol. Cell 2013, 49:751-758.
11. Goetz E.M., Ghandi M., Treacy D.J., Wagle N., Garraway L.A. ERK mutations confer resistance to mitogen-activated protein kinase pathway inhibitors. Cancer Res. 2014, 74:7079-7089.
12. Gorczynski M.J., Grembecka J., Zhou Y., Kong Y., Roudaia L., Douvas M.G., Newman M., Bielnicka I., Baber G., Corpora T., et al. Allosteric inhibition of the protein-protein interaction between the leukemia-associated proteins Runx1 and CBFbeta. Chem. Biol. 2007, 14:1186-1197.
13. Gramling M.W., Eischen C.M. Suppression of Ras/Mapk pathway signaling inhibits Myc-induced lymphomagenesis. Cell Death Differ. 2012, 19:1220-1227.
14. Holderfield M., Deuker M.M., McCormick F., McMahon M. Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat. Rev. Cancer 2014, 14:455-467.
15. Jameson K.L., Mazur P.K., Zehnder A.M., Zhang J., Zarnegar B., Sage J., Khavari P.A. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat. Med. 2013, 19:626-630.
16. Khokhlatchev A.V., Canagarajah B., Wilsbacher J., Robinson M., Atkinson M., Goldsmith E., Cobb M.H. Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation. Cell 1998, 93:605-615.
17. Lefloch R., Pouysségur J., Lenormand P. Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels. Mol. Cell. Biol. 2008, 28:511-527.
18. Little A.S., Balmanno K., Sale M.J., Newman S., Dry J.R., Hampson M., Edwards P.A., Smith P.D., Cook S.J. Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells. Sci. Signal. 2011, 4:ra17.
19. Little A.S., Smith P.D., Cook S.J. Mechanisms of acquired resistance to ERK1/2 pathway inhibitors. Oncogene 2013, 32:1207-1215.
20. Lozano J., Xing R., Cai Z., Jensen H.L., Trempus C., Mark W., Cannon R., Kolesnick R. Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice. Cancer Res. 2003, 63:4232-4238.
21. Lüscher B., Larsson L.G. The basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins: function and regulation. Oncogene 1999, 18:2955-2966.
22. Mao P., Hever M.P., Niemaszyk L.M., Haghkerdar J.M., Yanco E.G., Desai D., Beyrouthy M.J., Kerley-Hamilton J.S., Freemantle S.J., Spinella M.J. Serine/threonine kinase 17A is a novel p53 target gene and modulator of cisplatin toxicity and reactive oxygen species in testicular cancer cells. J. Biol. Chem. 2011, 286:19381-19391.
23. Matallanas D., Crespo P. New druggable targets in the Ras pathway?. Curr. Opin. Mol. Ther. 2010, 12:674-683.
24. Michailidou C., Jones M., Walker P., Kamarashev J., Kelly A., Hurlstone A.F. Dissecting the roles of Raf- and PI3K-signalling pathways in melanoma formation and progression in a zebrafish model. Dis. Model. Mech. 2009, 2:399-411.
25. Montagut C., Settleman J. Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett. 2009, 283:125-134.
26. Mooz J., Oberoi-Khanuja T.K., Harms G.S., Wang W., Jaiswal B.S., Seshagiri S., Tikkanen R., Rajalingam K. Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration. Sci. Signal. 2014, 7:ra73.
27. Morris E.J., Jha S., Restaino C.R., Dayananth P., Zhu H., Cooper A., Carr D., Deng Y., Jin W., Black S., et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013, 3:742-750.
28. Nazarian R., Shi H., Wang Q., Kong X., Koya R.C., Lee H., Chen Z., Lee M.K., Attar N., Sazegar H., et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 2010, 468:973-977.
29. Philipova R., Whitaker M. Active ERK1 is dimerized in vivo: bisphosphodimers generate peak kinase activity and monophosphodimers maintain basal ERK1 activity. J. Cell Sci. 2005, 118:5767-5776.
30. Pinto A., Crespo P. Analysis of ERKs' dimerization by electrophoresis. Methods Mol. Biol. 2010, 661:335-342.
31. Poulikakos P.I., Zhang C., Bollag G., Shokat K.M., Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010, 464:427-430.
32. Puig I., Chicote I., Tenbaum S.P., Arqués O., Herance J.R., Gispert J.D., Jimenez J., Landolfi S., Caci K., Allende H., et al. A personalized preclinical model to evaluate the metastatic potential of patient-derived colon cancer initiating cells. Clin. Cancer Res. 2013, 19:6787-6801.
33. Pylayeva-Gupta Y., Grabocka E., Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat. Rev. Cancer 2011, 11:761-774.
34. Solit D.B., Garraway L.A., Pratilas C.A., Sawai A., Getz G., Basso A., Ye Q., Lobo J.M., She Y., Osman I., et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006, 439:358-362.
35. Tenbaum S.P., Ordóñez-Morán P., Puig I., Chicote I., Arqués O., Landolfi S., Fernández Y., Herance J.R., Gispert J.D., Mendizabal L., et al. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat. Med. 2012, 18:892-901.
36. Wilsbacher J.L., Juang Y.C., Khokhlatchev A.V., Gallagher E., Binns D., Goldsmith E.J., Cobb M.H. Characterization of mitogen-activated protein kinase (MAPK) dimers. Biochemistry 2006, 45:13175-13182.