Depletion of FOXM1 via MET targeting underlies establishment of …clincancerres.aacrjournals.org/content/clincanres/early/2016/05/14/... · 1 Depletion of FOXM1 via MET targeting
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Depletion of FOXM1 via MET targeting underlies establishment of a DNA damage-induced senescence program in gastric cancer
Paola Francica1,2, Lluís Nisa1,2, Daniel M. Aebersold1,2, Rupert Langer3, Friedhelm Bladt4#,
Andree Blaukat4, Deborah M. Stroka2,5, María Rodríguez Martínez6, Yitzhak Zimmer1,2,
Michaela Medová1,2
Author Affiliations: 1 Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of
Bern, 3010 Bern, Switzerland 2 Department of Clinical Research, University of Bern, 3010 Bern, Switzerland 3 Institute of Pathology, University of Bern, 3010 Bern, Switzerland 4 Merck Serono Research & Development, Merck KGaA, Darmstadt, Germany 5 Department of Visceral Surgery, Inselspital, Bern University Hospital, and University of
Bern, 3010 Bern, Switzerland 6 IBM Research, Zurich Research Laboratory, Zurich, Switzerland #Current address: Bayer Pharma AG, Global Drug Discovery – Clinical Sciences, Experimental Medicine ONC, Berlin, Germany
Running Title: MET, FOXM1 and DNA damage-induced senescence
Keywords: MET, FOXM1, senescence, DNA damage, gastric cancer Corresponding author: Dr. Michaela Medová, Department of Radiation Oncology, Inselspital, Bern, Switzerland. Tel:
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
1. Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11:834-48. 2. Ma PC, Tretiakova MS, MacKinnon AC, Ramnath N, Johnson C, Dietrich S, et al. Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer. 2008;47:1025-37. 3. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359-86. 4. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005;241:27-39. 5. Liu YJ, Shen D, Yin X, Gavine P, Zhang T, Su X, et al. HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma. Br J Cancer. 2014;110:1169-78. 6. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894-902. 7. An X, Wang F, Shao Q, Wang FH, Wang ZQ, Chen C, et al. MET amplification is not rare and predicts unfavorable clinical outcomes in patients with recurrent/metastatic gastric cancer after chemotherapy. Cancer. 2014;120:675-82. 8. Lee HE, Kim MA, Lee HS, Jung EJ, Yang HK, Lee BL, et al. MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome. Br J Cancer. 2012;107:325-33. 9. Graziano F, Galluccio N, Lorenzini P, Ruzzo A, Canestrari E, D'Emidio S, et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol. 2011;29:4789-95. 10. Smolen GA, Sordella R, Muir B, Mohapatra G, Barmettler A, Archibald H, et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc Natl Acad Sci U S A. 2006;103:2316-21. 11. Feng Y, Ma PC. Anti-MET targeted therapy has come of age: the first durable complete response with MetMAb in metastatic gastric cancer. Cancer Discov. 2011;1:550-4. 12. Catenacci DV, Henderson L, Xiao SY, Patel P, Yauch RL, Hegde P, et al. Durable complete response of metastatic gastric cancer with anti-Met therapy followed by resistance at recurrence. Cancer Discov. 2011;1:573-9. 13. Peters S, Adjei AA. MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol. 2012;9:314-26. 14. Medova M, Aebersold DM, Blank-Liss W, Streit B, Medo M, Aebi S, et al. MET Inhibition Results in DNA Breaks and Synergistically Sensitizes Tumor Cells to DNA-Damaging Agents Potentially by Breaching a Damage-Induced Checkpoint Arrest. Genes Cancer. 2010;1:1053-62. 15. Medova M, Aebersold DM, Zimmer Y. The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response-Biological and Clinical Aspects. Cancers (Basel). 2013;6:1-27. 16. Ganapathipillai SS, Medova M, Aebersold DM, Manley PW, Berthou S, Streit B, et al. Coupling of mutated Met variants to DNA repair via Abl and Rad51. Cancer Res. 2008;68:5769-77. 17. Medova M, Aebersold DM, Zimmer Y. MET inhibition in tumor cells by PHA665752 impairs homologous recombination repair of DNA double strand breaks. Int J Cancer. 2012;130:728-34. 18. d'Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer. 2008;8:512-22. 19. Azad A, Jackson S, Cullinane C, Natoli A, Neilsen PM, Callen DF, et al. Inhibition of DNA-dependent protein kinase induces accelerated senescence in irradiated human cancer cells. Mol Cancer Res. 2011;9:1696-707.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
20. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585-621. 21. Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130:223-33. 22. Collado M, Serrano M. Senescence in tumours: evidence from mice and humans. Nat Rev Cancer. 2010;10:51-7. 23. Nardella C, Clohessy JG, Alimonti A, Pandolfi PP. Pro-senescence therapy for cancer treatment. Nat Rev Cancer. 2011;11:503-11. 24. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res. 2002;62:1876-83. 25. Myatt SS, Lam EW. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer. 2007;7:847-59. 26. Koo CY, Muir KW, Lam EW. FOXM1: From cancer initiation to progression and treatment. Biochim Biophys Acta. 2012;1819:28-37. 27. Teh MT. FOXM1 coming of age: time for translation into clinical benefits? Front Oncol. 2012;2:146. 28. Monteiro LJ, Khongkow P, Kongsema M, Morris JR, Man C, Weekes D, et al. The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment. Oncogene. 2013;32:4634-45. 29. Alvarez-Fernandez M, Medema RH. Novel functions of FoxM1: from molecular mechanisms to cancer therapy. Front Oncol. 2013;3:30. 30. Khongkow P, Karunarathna U, Khongkow M, Gong C, Gomes AR, Yague E, et al. FOXM1 targets NBS1 to regulate DNA damage-induced senescence and epirubicin resistance. Oncogene. 2013. 31. Britschgi C, Rizzi M, Grob TJ, Tschan MP, Hugli B, Reddy VA, et al. Identification of the p53 family-responsive element in the promoter region of the tumor suppressor gene hypermethylated in cancer 1. Oncogene. 2006;25:2030-9. 32. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92:9363-7. 33. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139-40. 34. Roninson IB. Tumor cell senescence in cancer treatment. Cancer Res. 2003;63:2705-15. 35. Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell. 2002;109:335-46. 36. Adams PD. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol Cell. 2009;36:2-14. 37. Olsen CL, Gardie B, Yaswen P, Stampfer MR. Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and is overcome in immortal cells during conversion. Oncogene. 2002;21:6328-39. 38. Furlan A, Stagni V, Hussain A, Richelme S, Conti F, Prodosmo A, et al. Abl interconnects oncogenic Met and p53 core pathways in cancer cells. Cell Death Differ. 2011;18:1608-16. 39. Nabeya Y, Loganzo F, Jr., Maslak P, Lai L, de Oliveira AR, Schwartz GK, et al. The mutational status of p53 protein in gastric and esophageal adenocarcinoma cell lines predicts sensitivity to chemotherapeutic agents. Int J Cancer. 1995;64:37-46. 40. Ku JL, Park JG. Biology of SNU cell lines. Cancer Res Treat. 2005;37:1-19. 41. Li SK, Smith DK, Leung WY, Cheung AM, Lam EW, Dimri GP, et al. FoxM1c counteracts oxidative stress-induced senescence and stimulates Bmi-1 expression. J Biol Chem. 2008;283:16545-53. 42. Takahashi T, Saikawa Y, Kitagawa Y. Gastric cancer: current status of diagnosis and treatment. Cancers (Basel). 2013;5:48-63.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
43. Hack SP, Bruey JM, Koeppen H. HGF/MET-directed therapeutics in gastroesophageal cancer: a review of clinical and biomarker development. Oncotarget. 2014;5:2866-80. 44. Bladt F, Faden B, Friese-Hamim M, Knuehl C, Wilm C, Fittschen C, et al. EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors. Clin Cancer Res. 2013;19:2941-51. 45. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993;362:847-9. 46. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120:513-22. 47. Wang M, Morsbach F, Sander D, Gheorghiu L, Nanda A, Benes C, et al. EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks. Cancer Res. 2011;71:6261-9. 48. Havelka AM, Berndtsson M, Olofsson MH, Shoshan MC, Linder S. Mechanisms of action of DNA-damaging anticancer drugs in treatment of carcinomas: is acute apoptosis an "off-target" effect? Mini Rev Med Chem. 2007;7:1035-9. 49. Zeng J, Wang L, Li Q, Li W, Bjorkholm M, Jia J, et al. FoxM1 is up-regulated in gastric cancer and its inhibition leads to cellular senescence, partially dependent on p27 kip1. J Pathol. 2009;218:419-27. 50. Ma RY, Tong TH, Leung WY, Yao KM. Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1. Methods Mol Biol. 2010;647:113-23.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987
Published OnlineFirst May 16, 2016.Clin Cancer Res P. Francica, L. Nisa, Daniel M Aebersold, et al. cancerof a DNA damage-induced senescence program in gastric Depletion of FOXM1 via MET targeting underlies establishment
Updated version
10.1158/1078-0432.CCR-15-2987doi:
Access the most recent version of this article at:
To order reprints of this article or to subscribe to the journal, contact the AACR Publications
Permissions
Rightslink site. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC)
.http://clincancerres.aacrjournals.org/content/early/2016/05/14/1078-0432.CCR-15-2987To request permission to re-use all or part of this article, use this link
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 16, 2016; DOI: 10.1158/1078-0432.CCR-15-2987