RPL22L1 induction in colorectal cancer is associated with poor prognosis and 5-FU resistance


Autoři: Shuyun Rao aff001;  Suraj Peri aff002;  Jens Hoffmann aff003;  Kathy Q. Cai aff004;  Bryan Harris aff002;  Michele Rhodes aff002;  Denise C. Connolly aff005;  Joseph R. Testa aff004;  David L. Wiest aff002
Působiště autorů: Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC, United States of America aff001;  Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, United States of America aff002;  Experimental Pharmacology & Oncology Berlin-Buch GMBH, Berlin-Buch, Germany aff003;  Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, United States of America aff004;  Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222392

Souhrn

We have previously demonstrated that loss of the tumor suppressive activity of ribosomal protein (RP) RPL22 predisposes to development of leukemia in mouse models and aggressive disease in human patients; however, the role of RPL22 in solid tumors, specifically colorectal cancer (CRC), had not been explored. We report here that RPL22 is either deleted or mutated in 36% of CRC and provide new insights into its mechanism of action. Indeed, Rpl22 inactivation causes the induction of its highly homologous paralog, RPL22L1, which serves as a driver of cell proliferation and anchorage-independent growth in CRC cells. Moreover, RPL22L1 protein is highly expressed in patient CRC samples and correlates with poor survival. Interestingly, the association of high RPL22L1 expression with poor prognosis appears to be linked to resistance to 5-Fluorouracil, which is a core component of most CRC therapeutic regimens. Indeed, in an avatar trial, we found that human CRC samples that were unresponsive to 5-Fluorouracil in patient-derived xenografts exhibited elevated expression levels of RPL22L1. This link between RPL22L1 induction and 5-Fluorouracil resistance appears to be causal, because ectopic expression or knockdown of RPL22L1 in cell lines increases and decreases 5-Fluorouracil resistance, respectively, and this is associated with changes in expression of the DNA-repair genes, MGMT and MLH1. In summary, our data suggest that RPL22L1 might be a prognostic marker in CRC and predict 5-FU responsiveness.

Klíčová slova:

Cancer treatment – Cell proliferation – Colon – Colorectal cancer – Epithelial cells – Immunohistochemistry techniques – Nuclear staining – Colon adenocarcinoma


Zdroje

1. Kenmochi N. [Ribosomopathies—defective ribosome biogenesis and diseases]. Seikagaku. 2013;85(10):909–15. Epub 2014/01/08. 24392590.

2. Rao S, Lee SY, Gutierrez A, Perrigoue J, Thapa RJ, Tu Z, et al. Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood. 2012;120(18):3764–73. Epub 2012/09/15. doi: 10.1182/blood-2012-03-415349 22976955; PubMed Central PMCID: PMC3488889.

3. Zhang Y, Duc AC, Rao S, Sun XL, Bilbee AN, Rhodes M, et al. Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs. Dev Cell. 2013;24(4):411–25. Epub 2013/03/02. doi: 10.1016/j.devcel.2013.01.018 23449473; PubMed Central PMCID: PMC3586312.

4. Anderson SJ, Lauritsen JP, Hartman MG, Foushee AM, Lefebvre JM, Shinton SA, et al. Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity. 2007;26(6):759–72. Epub 2007/06/09. doi: 10.1016/j.immuni.2007.04.012 17555992.

5. Rao S, Cai KQ, Stadanlick JE, Greenberg-Kushnir N, Solanki-Patel N, Lee SY, et al. Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma. Cancer research. 2016;76(11):3387–96. doi: 10.1158/0008-5472.CAN-15-2698 27197189; PubMed Central PMCID: PMC4891229.

6. Novetsky AP, Zighelboim I, Thompson DM Jr., Powell MA, Mutch DG, Goodfellow PJ. Frequent mutations in the RPL22 gene and its clinical and functional implications. Gynecol Oncol. 2013;128(3):470–4. Epub 2012/11/07. doi: 10.1016/j.ygyno.2012.10.026 23127973; PubMed Central PMCID: PMC3845021.

7. Ferreira AM, Tuominen I, van Dijk-Bos K, Sanjabi B, van der Sluis T, van der Zee AG, et al. High frequency of RPL22 mutations in microsatellite-unstable colorectal and endometrial tumors. Hum Mutat. 2014;35(12):1442–5. Epub 2014/09/10. doi: 10.1002/humu.22686 25196364.

8. Zou Y, Huang MZ, Liu FY, Yang BC, Wang LQ, Wang F, et al. Absence of and hotspot mutations in patients with various subtypes of ovarian carcinomas. Biomed Rep. 2015;3(1):33–7. Epub 2014/12/04. doi: 10.3892/br.2014.378 25469243; PubMed Central PMCID: PMC4251111.

9. Zheng S, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA, et al. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma. Cancer cell. 2016;30(2):363. Epub 2016/08/10. doi: 10.1016/j.ccell.2016.07.013 27505681.

10. Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, Nishihara R, et al. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma. Cell Rep. 2016. doi: 10.1016/j.celrep.2016.03.075 27149842; PubMed Central PMCID: PMC4850357.

11. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30. doi: 10.3322/caac.21387 28055103.

12. Midgley RS, Yanagisawa Y, Kerr DJ. Evolution of nonsurgical therapy for colorectal cancer. Nat Clin Pract Gastroenterol Hepatol. 2009;6(2):108–20. doi: 10.1038/ncpgasthep1337 19153564.

13. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714–26. doi: 10.1038/nrc3599 24060863.

14. Gustavsson B, Carlsson G, Machover D, Petrelli N, Roth A, Schmoll HJ, et al. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer. 2015;14(1):1–10. doi: 10.1016/j.clcc.2014.11.002 25579803.

15. Fichtner I, Slisow W, Gill J, Becker M, Elbe B, Hillebrand T, et al. Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas. European journal of cancer (Oxford, England: 1990). 2004;40(2):298–307. doi: 10.1016/j.ejca.2003.10.011 14728946.

16. Liu H, Xiao F, Serebriiskii IG, O'Brien SW, Maglaty MA, Astsaturov I, et al. Network analysis identifies an HSP90-central hub susceptible in ovarian cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013;19(18):5053–67. Epub 2013/08/01. doi: 10.1158/1078-0432.Ccr-13-1115 23900136; PubMed Central PMCID: PMC3778161.

17. Mehra R, Zhu F, Yang DH, Cai KQ, Weaver J, Singh MK, et al. Quantification of excision repair cross-complementing group 1 and survival in p16-negative squamous cell head and neck cancers. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013;19(23):6633–43. doi: 10.1158/1078-0432.CCR-13-0152 24088734; PubMed Central PMCID: PMC4045641.

18. Prudnikova TY, Villamar-Cruz O, Rawat SJ, Cai KQ, Chernoff J. Effects of p21-activated kinase 1 inhibition on 11q13-amplified ovarian cancer cells. Oncogene. 2016;35(17):2178–85. doi: 10.1038/onc.2015.278 26257058; PubMed Central PMCID: PMC5125076.

19. Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–7. doi: 10.1038/nature11252 22810696; PubMed Central PMCID: PMC3401966.

20. O'Leary MN, Schreiber KH, Zhang Y, Duc AC, Rao S, Hale JS, et al. The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1. PLoS Genet. 2013;9(8):e1003708. Epub 2013/08/31. doi: 10.1371/journal.pgen.1003708 23990801; PubMed Central PMCID: PMC3750023.

21. Fischer F, Baerenfaller K, Jiricny J. 5-Fluorouracil is efficiently removed from DNA by the base excision and mismatch repair systems. Gastroenterology. 2007;133(6):1858–68. Epub 2007/12/07. doi: 10.1053/j.gastro.2007.09.003 18054558.

22. Meyers M, Wagner MW, Hwang HS, Kinsella TJ, Boothman DA. Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer research. 2001;61(13):5193–201. Epub 2001/06/30. 11431359.

23. Jover R, Zapater P, Castells A, Llor X, Andreu M, Cubiella J, et al. The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status. European journal of cancer (Oxford, England: 1990). 2009;45(3):365–73. doi: 10.1016/j.ejca.2008.07.016 18722765.

24. Kishi K, Doki Y, Yano M, Yasuda T, Fujiwara Y, Takiguchi S, et al. Reduced MLH1 expression after chemotherapy is an indicator for poor prognosis in esophageal cancers. Clin Cancer Res. 2003;9(12):4368–75. 14555508.

25. Cohen R, Cervera P, Svrcek M, Pellat A, Dreyer C, de Gramont A, et al. BRAF-Mutated Colorectal Cancer: What Is the Optimal Strategy for Treatment? Curr Treat Options Oncol. 2017;18(2):9. doi: 10.1007/s11864-017-0453-5 28214977.

26. Konduri SD, Ticku J, Bobustuc GC, Sutphin RM, Colon J, Isley B, et al. Blockade of MGMT expression by O6 benzyl guanine leads to inhibition of pancreatic cancer growth and induction of apoptosis. Clinical cancer research: an official journal of the American Association for Cancer Research. 2009;15(19):6087–95. Epub 2009/10/01. doi: 10.1158/1078-0432.Ccr-09-0887 19789303.

27. Murakami J, Lee YJ, Kokeguchi S, Tsujigiwa H, Asaumi J, Nagatsuka H, et al. Depletion of O6-methylguanine-DNA methyltransferase by O6-benzylguanine enhances 5-FU cytotoxicity in colon and oral cancer cell lines. Oncology reports. 2007;17(6):1461–7. Epub 2007/05/10. 17487405.

28. Lonardi S, Sobrero A, Rosati G, Di Bartolomeo M, Ronzoni M, Aprile G, et al. Phase III trial comparing 3–6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial. Annals of oncology: official journal of the European Society for Medical Oncology. 2016;27(11):2074–81. Epub 2016/10/30. doi: 10.1093/annonc/mdw404 27573560.

29. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. The New England journal of medicine. 2004;350(23):2343–51. Epub 2004/06/04. doi: 10.1056/NEJMoa032709 15175436.

30. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. The Lancet Oncology. 2015;16(13):1306–15. Epub 2015/09/05. doi: 10.1016/S1470-2045(15)00122-9 26338525.

31. Copija A, Waniczek D, Witkos A, Walkiewicz K, Nowakowska-Zajdel E. Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients. International journal of molecular sciences. 2017;18(1). Epub 2017/01/10. doi: 10.3390/ijms18010107 28067827; PubMed Central PMCID: PMC5297741.

32. Klingbiel D, Saridaki Z, Roth AD, Bosman FT, Delorenzi M, Tejpar S. Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Annals of oncology: official journal of the European Society for Medical Oncology. 2015;26(1):126–32. Epub 2014/11/02. doi: 10.1093/annonc/mdu499 25361982.

33. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. The New England journal of medicine. 2003;349(3):247–57. doi: 10.1056/NEJMoa022289 12867608; PubMed Central PMCID: PMC3584639.

34. Sinicrope FA, Foster NR, Thibodeau SN, Marsoni S, Monges G, Labianca R, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 2011;103(11):863–75. doi: 10.1093/jnci/djr153 21597022; PubMed Central PMCID: PMC3110173.

35. Stelloo E, Jansen AML, Osse EM, Nout RA, Creutzberg CL, Ruano D, et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Annals of oncology: official journal of the European Society for Medical Oncology. 2017;28(1):96–102. Epub 2016/10/16. doi: 10.1093/annonc/mdw542 27742654.

36. Nagasaka T, Goel A, Notohara K, Takahata T, Sasamoto H, Uchida T, et al. Methylation pattern of the O6-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis. Int J Cancer. 2008;122(11):2429–36. doi: 10.1002/ijc.23398 18240147; PubMed Central PMCID: PMC2851179.

37. Amatu A, Sartore-Bianchi A, Moutinho C, Belotti A, Bencardino K, Chirico G, et al. Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II study for metastatic colorectal cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013;19(8):2265–72. doi: 10.1158/1078-0432.CCR-12-3518 23422094.

38. Minoo P. Toward a Molecular Classification of Colorectal Cancer: The Role of MGMT. Front Oncol. 2013;3:266. doi: 10.3389/fonc.2013.00266 24151575; PubMed Central PMCID: PMC3798865.

39. Shima K, Morikawa T, Baba Y, Nosho K, Suzuki M, Yamauchi M, et al. MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers. Cancer Causes Control. 2011;22(2):301–9. doi: 10.1007/s10552-010-9698-z 21140203; PubMed Central PMCID: PMC3278857.

40. Kitange GJ, Carlson BL, Schroeder MA, Grogan PT, Lamont JD, Decker PA, et al. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro Oncol. 2009;11(3):281–91. doi: 10.1215/15228517-2008-090 18952979; PubMed Central PMCID: PMC2718972.

41. Zhang Y, O'Leary MN, Peri S, Wang M, Zha J, Melov S, et al. Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing. Cell Rep. 2017;18(2):545–56. Epub 2017/01/12. doi: 10.1016/j.celrep.2016.12.034 28076796; PubMed Central PMCID: PMC5234864.


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