Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

BMC Cancer

Volumn 13, Issue , 2013, Pages

  Golubovskaya, Vita M ^a   Ho, Baotran ^a   Zheng, Min ^b   Magis, Andrew ^c   Ostrov, David ^c   Morrison, Carl ^a   Cance, William G ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

^b University of Oklahoma Cell Sciences Center   (United States)

^c UNIVERSITY OF FLORIDA   (United States)

Author keywords

Apoptosis; Focal adhesion kinase; p21; p53Cancer; Small molecule; Tumor

Indexed keywords

1 BENZYL 15,3,5,7 TETRAAZATRICYCLO[3.3.1.1 3,7]DECANE; ANTINEOPLASTIC AGENT; DOXORUBICIN; FLUOROURACIL; FOCAL ADHESION KINASE; PROTEIN BAX; PROTEIN MDM2; PROTEIN P21; PROTEIN P53; UNCLASSIFIED DRUG; ANTINEOPLASTIC ANTIBIOTIC; ANTINEOPLASTIC ANTIMETABOLITE; FOCAL ADHESION KINASE 1; MOLECULAR LIBRARY; TP53 PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CANCER INHIBITION; CELL VIABILITY; CLONOGENESIS; COLON CANCER; CONTROLLED STUDY; DRUG SENSITIZATION; FEMALE; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BREAST NEOPLASMS; CELL CYCLE; CELL PROLIFERATION; COLONIC NEOPLASMS; DRUG EFFECTS; DRUG SCREENING; ENZYME IMMUNOASSAY; FLOW CYTOMETRY; GENETICS; IMMUNOPRECIPITATION; METABOLISM; MOLECULAR LIBRARY; MUTATION; NUDE MOUSE; PATHOLOGY; PHARMACOLOGY; PROTEIN CONFORMATION; TRANSCRIPTION INITIATION; TUMOR CELL CULTURE; WESTERN BLOTTING;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL CYCLE; CELL PROLIFERATION; COLONIC NEOPLASMS; DOXORUBICIN; FEMALE; FLOW CYTOMETRY; FLUOROURACIL; FOCAL ADHESION KINASE 1; HUMANS; IMMUNOENZYME TECHNIQUES; IMMUNOPRECIPITATION; MICE; MICE, NUDE; MUTATION; PROTEIN CONFORMATION; SMALL MOLECULE LIBRARIES; TRANSCRIPTIONAL ACTIVATION; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84880013271     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-13-342     Document Type: Article

References (50)

1. Hanks SK, Polte TR. Signaling through focal adhesion kinase. Bioessays 1997, 19:137-145. 10.1002/bies.950190208, 9046243.
2. Mitra SK, Schlaepfer DD. Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 2006, 18:516-523. 10.1016/j.ceb.2006.08.011, 16919435.
3. McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC. The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer 2005, 5:505-515. 10.1038/nrc1647, 16069815.
4. Schaller MD Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci 2010, 123:1007-1013. 10.1242/jcs.045112, 20332118, Schaller MD.
5. Guan JL. Role of focal adhesion kinase in integrin signaling. Int J Biochem Cell Biol 1997, 29:1085-1096. 10.1016/S1357-2725(97)00051-4, 9416004.
6. Zhao X, Guan JL. Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Adv Drug Deliv Rev 2011, 63:610-615. 10.1016/j.addr.2010.11.001, 3132829, 21118706.
7. Cance WG, Harris JE, Iacocca MV, Roche E, Yang X, Chang J, Simkins S, Xu L. Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes. Clin Cancer Res 2000, 6:2417-2423.
8. Cance WG, Liu ET. Protein kinases in human breast cancer. Breast Cancer Res Treat 1995, 35:105-114. 10.1007/BF00694751, 7612897.
9. Owens LV, Xu L, Craven RJ, Dent GA, Weiner TM, Kornberg L, Liu ET, Cance WG. Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res 1995, 55:2752-2755.
10. Lark AL, Livasy CA, Calvo B, Caskey L, Moore DT, Yang X, Cance WG. Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses. Clin Cancer Res 2003, 9:215-222.
11. Lightfoot HM, Lark A, Livasy CA, Moore DT, Cowan D, Dressler L, Craven RJ, Cance WG. Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis. Breast Cancer Res Treat 2004, 88:109-116. 10.1007/s10549-004-1022-8, 15564794.
12. Golubovskaya VM, Cance WG. Focal adhesion kinase and p53 signaling in cancer cells. Int Rev Cytol 2007, 263:103-153.
13. Golubovskaya V, Kaur A, Cance W. Cloning and characterization of the promoter region of human focal adhesion kinase gene: nuclear factor kappa B and p53 binding sites*1. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 2004 2004, 1678:111-125.
14. Golubovskaya VM, Conway-Dorsey K, Edmiston SN, Tse CK, Lark AA, Livasy CA, Moore D, Millikan RC, Cance WG. FAK overexpression and p53 mutations are highly correlated in human breast cancer. Int J Cancer 2009, 125:1735-1738. 10.1002/ijc.24486, 2773794, 19521985.
15. Cance WG, Golubovskaya VM. Focal adhesion kinase versus p53: apoptosis or survival?. Sci Signal 2008, 1:pe22. 10.1126/stke.120pe22, 18493017.
16. Anaganti S, Fernandez-Cuesta L, Langerod A, Hainaut P, Olivier M. p53-Dependent repression of focal adhesion kinase in response to estradiol in breast cancer cell-lines. Cancer Lett 2011, 300:215-224. 10.1016/j.canlet.2010.10.008, 21071137.
17. Golubovskaya VM, Cance W. Focal adhesion kinase and p53 signal transduction pathways in cancer. Front Biosci 2010, 15:901-912. 10.2741/3653, 3136041, 20515733.
18. Golubovskaya VM, Finch R, Cance WG. Direct Interaction of the N-terminal Domain of Focal Adhesion Kinase with the N-terminal Transactivation Domain of p53. J Biol Chem 2005, 280:25008-25021. 10.1074/jbc.M414172200, 15855171.
19. Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D. Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell 2008, 29:9-22. 10.1016/j.molcel.2007.11.031, 2234035, 18206965.
20. Golubovskaya VM, Finch R, Zheng M, Kurenova EV, Cance WG. The 7-amino-acid site in the proline-rich region of the N-terminal domain of p53 is involved in the interaction with FAK and is critical for p53 functioning. Biochem J 2008, 411:151-160. 10.1042/BJ20071657, 18215142.
21. Frame MC, Patel H, Serrels B, Lietha D, Eck MJ. The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol 2010, 11:802-814. 10.1038/nrm2996, 20966971.
22. Vassilev LT. p53 Activation by small molecules: application in oncology. J Med Chem 2005, 48:4491-4499. 10.1021/jm058174k, 15999986.
23. Hainaut P, Hollstein M. p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 2000, 77:81-137.
24. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004, 303:844-848. 10.1126/science.1092472, 14704432.
25. Galatin PS, Abraham DJ. A nonpeptidic sulfonamide inhibits the p53-mdm2 interaction and activates p53-dependent transcription in mdm2-overexpressing cells. J Med Chem 2004, 47:4163-4165. 10.1021/jm034182u, 15293988.
26. Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004, 10:1321-1328. 10.1038/nm1146, 15558054.
27. Yin H, Lee GI, Park HS, Payne GA, Rodriguez JM, Sebti SM, Hamilton AD. Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. Angew Chem Int Ed Engl 2005, 44:2704-2707. 10.1002/anie.200462316, 15765497.
28. Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR, et al. Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J Med Chem 2005, 48:909-912. 10.1021/jm049137g, 15715460.
29. Ding K, Lu Y, Nikolovska-Coleska Z, Wang G, Qiu S, Shangary S, Gao W, Qin D, Stuckey J, Krajewski K, et al. Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. J Med Chem 2006, 49:3432-3435. 10.1021/jm051122a, 16759082.
30. Golubovskaya VM, Cance WG. FAK AND P53 Protein Interactions. Anticancer Agents Med Chem 2013, 13:576-580. 10.2174/1871520611313040006, 3625462, 22934707.
31. Ceccarelli DF, Song HK, Poy F, Schaller MD, Eck MJ. Crystal structure of the FERM domain of focal adhesion kinase. J Biol Chem 2006, 281:252-259.
32. Golubovskaya V, Ho B, Zheng M, Magis A, Ostrov D, Cance W. Mitoxantrone Targets The ATP-Binding Site Of FAK, Binds The FAK Kinase Domain And Decreases FAK, Pyk-2, C-Src, And IGF-1R, Pyk-2 In Vitro Kinase Activities. Anticancer Agents Med Chem 2013, 13:546-554. 10.2174/1871520611313040003, 3625494, 22292772.
33. Golubovskaya V, Palma NL, Zheng M, Ho B, Magis A, Ostrov D, Cance WG. A Small-Molecule Inhibitor, 5′-O-Tritylthymidine, Targets FAK And Mdm-2 Interaction, And Blocks Breast And Colon Tumorigenesis In Vivo. Anticancer Agents Med Chem 2013, 13:532-545. 10.2174/1871520611313040002, 3625481, 22292771.
34. Kelley LA, Sternberg MJ. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 2009, 4:363-371.
35. Di Lello P, Jenkins LM, Jones TN, Nguyen BD, Hara T, Yamaguchi H, Dikeakos JD, Appella E, Legault P, Omichinski JG. Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53. Mol Cell 2006, 22:731-740. 10.1016/j.molcel.2006.05.007, 16793543.
36. Holbeck SL. Update on NCI in vitro drug screen utilities. Eur J Cancer 2004, 40:785-793. 10.1016/j.ejca.2003.11.022, 15120034.
37. Irwin JJ, Sterling T, Mysinger MM, Bolstad ES, Coleman RG. ZINC: A Free Tool to Discover Chemistry for Biology. J Chem Inf Model 2012, 52:1757-1768. [Epub ahead of print].
38. Noorwez SM, Ostrov DA, McDowell JH, Krebs MP, Kaushal S. A high-throughput screening method for small-molecule pharmacologic chaperones of misfolded rhodopsin. Invest Ophthalmol Vis Sci 2008, 49:3224-3230. 10.1167/iovs.07-1539, 18378578.
39. Golubovskaya VM, Nyberg C, Zheng M, Kweh F, Magis A, Ostrov D, Cance WG. A Small Molecule Inhibitor, 1,2,4,5-Benzenetetraamine Tetrahydrochloride, Targeting the Y397 Site of Focal Adhesion Kinase Decreases Tumor Growth. J Med Chem 2008, 51:7405-7416. 10.1021/jm800483v, 2662449, 18989950.
40. Golubovskaya V, Beviglia L, Xu LH, Earp HS, Craven R, Cance W. Dual inhibition of focal adhesion kinase and epidermal growth factor receptor pathways cooperatively induces death receptor-mediated apoptosis in human breast cancer cells. J Biol Chem 2002, 277:38978-38987. 10.1074/jbc.M205002200, 12167618.
41. Frisch SM. Evidence for a function of death-receptor-related, death-domain- containing proteins in anoikis. Curr Biol 1999, 9:1047-1049. 10.1016/S0960-9822(99)80455-2, 10508612.
42. Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 1994, 124:619-626. 10.1083/jcb.124.4.619, 2119917, 8106557.
43. Kurenova E, Xu L-H, Yang X, Baldwin AS, Craven RJ, Hanks SK, Liu Z-G, Cance WG. Focal Adhesion Kinase Suppresses Apoptosis by Binding to the Death Domain of Receptor-Interacting Protein. Mol Cell Biol 2004, 24:4361-4371. 10.1128/MCB.24.10.4361-4371.2004, 400455, 15121855.
44. Kweh F, Zheng M, Kurenova E, Wallace M, Golubovskaya V, Cance WG. Neurofibromin physically interacts with the N-terminal domain of focal adhesion kinase. Mol Carcinog 2009, 48:1005-1017. 10.1002/mc.20552, 2783617, 19479903.
45. Vassilev LT. Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics. Cell Cycle 2004, 3:419-421.
46. Lupertz R, Watjen W, Kahl R, Chovolou Y. Dose- and time-dependent effects of doxorubicin on cytotoxicity, cell cycle and apoptotic cell death in human colon cancer cells. Toxicology 2010, 271:115-121. 10.1016/j.tox.2010.03.012, 20346999.
47. Corsi JM, Houbron C, Billuart P, Brunet I, Bouvree K, Eichmann A, Girault JA, Enslen H. Autophosphorylation-independent and dependent functions of Focal Adhesion Kinase during development. J Biol Chem 2009, 284:34764-34776.
48. Fan H, Zhao X, Sun S, Luo M, Guan JL. Focal adhesion kinase scaffolding function to mediate endophilin A2 phosphorylation promotes epithelial-mesenchymal transition and mammary cancer stem cell activities in vivo. J Biol Chem 2013, 288:3322-3333. [Epub ahead pf print], 10.1074/jbc.M112.420497, 23255596.
49. Lim ST, Chen XL, Tomar A, Miller NL, Yoo J, Schlaepfer DD. Knockin mutation reveals an essential role for focal adhesion kinase (FAK) activity in blood vessel morphogenesis, cell motility-polarity, but not cell proliferation. J Biol Chem 2010, 285:21526-21536. 10.1074/jbc.M110.129999, 2898428, 20442405.
50. Illc D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T, et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 1995, 377:539-544. 10.1038/377539a0, 7566154.