Phosphorylation of ribosomal protein S6 attenuates DNA damage and tumor suppression during development of pancreatic cancer

Cancer Research

Volumn 73, Issue 6, 2013, Pages 1811-1820

  Khalaileh, Abed ^a,b   Dreazen, Avigail ^a   Khatib, Areej ^c   Apel, Roy ^a   Swisa, Avital ^a   Kidess Bassir, Norma ^a   Maitra, Anirban ^d   Meyuhas, Oded ^a   Dor, Yuval ^a   Zamir, Gideon ^b  

^a HEBREW UNIVERSITY   (Israel)

^b HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^c Augusta Victoria Hospital   (Israel)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7,12 DIMETHYLBENZ[A]ANTHRACENE; BIOLOGICAL MARKER; GAMMA HISTONE H2AX; HISTONE H2AX; MUTANT PROTEIN; PROTEIN P53; PROTEIN S6; PROTEIN TRP53BP1; RAPAMYCIN; UNCLASSIFIED DRUG;

ACINAR CELL; ACINAR DUCTAL METAPLASIA; ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER GROWTH; CANCER INHIBITION; CARCINOGENESIS; CONTROLLED STUDY; DNA DAMAGE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; GENE EXPRESSION; HETEROZYGOSITY; METAPLASIA; MOUSE; NONHUMAN; ONCOGENE K RAS; PANCREAS CANCER; PRIORITY JOURNAL;

ANIMALS; BASE SEQUENCE; DNA DAMAGE; DNA PRIMERS; MICE; MICE, INBRED C57BL; MICE, INBRED ICR; MICE, KNOCKOUT; PANCREATIC NEOPLASMS; PHOSPHORYLATION; POLYMERASE CHAIN REACTION; RIBOSOMAL PROTEIN S6; SIROLIMUS;

EID: 84875448111     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-2014     Document Type: Article

References (50)

1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet 2011;378:607-20.
2. Stanger BZ, Dor Y. Dissecting the cellular origins of pancreatic cancer. Cell Cycle 2006;5:43-6.
3. Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, Crowley D, et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 2009;16:379-89.
4. Morris JPt, Cano DA, Sekine S, Wang SC, Hebrok M. Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J Clin Invest 2010;120:508-20.
5. De La OJ, Emerson LL, Goodman JL, Froebe SC, Illum BE, Curtis AB, et al. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc Natl Acad Sci U S A 2008;105: 18907-12.
6. Prevot PP, Simion A, Grimont A, Colletti M, Khalaileh A, Van den Steen G, et al. Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia. Gut 2012;61:1723-32.
7. Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 2003;17: 3112-26.
8. Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 2007;11:291-302.
9. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005;7:469-83.
10. Guerra C, Collado M, Navas C, Schuhmacher AJ, Hernandez-Porras I, Canamero M, et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell 2011;19:728-39.
11. Caldwell ME, Denicola GM, Martins CP, Jacobetz MA, Maitra A, Hruban RH, et al. Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer. Oncogene 2012;31: 1599-608.
12. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, et al. Hedgehog is an early and latemediator of pancreatic cancer tumorigenesis. Nature 2003;425:851-6.
13. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009;324:1457-61.
14. Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ. Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br J Cancer 2003;89:2110-5.
15. Ying H, Elpek KG, Vinjamoori A, Zimmerman SM, Chu GC, Yan H, et al. Pten is a major tumor suppressor in pancreatic ductal adenocarcinoma and regulates an NF-kappaB-cytokine network. Cancer Discov 2011; 1:158-69.
16. Stanger BZ, Stiles B, Lauwers GY, Bardeesy N, Mendoza M, Wang Y, et al. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 2005;8:185-95.
17. Hill R, Calvopina JH, Kim C, Wang Y, Dawson DW, Donahue TR, et al. PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res 2010;70:7114-24.
18. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;12:21-35.
19. Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, et al. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 2010;328:1172-6.
20. Mishra R, Miyamoto M, Yoshioka T, Ishikawa K, Matsumura Y, Shoji Y, et al. Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo. Int J Oncol 2009;34: 1231-40.
21. Mirzoeva OK, Hann B, Hom YK, Debnath J, Aftab D, Shokat K, et al. Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K-mTOR pathway in pancreatic adenocarcinoma. J Mol Med (Berl) 2011;89:877-89.
22. Awasthi N, Yen PL, Schwarz MA, Schwarz RE. The efficacy of a novel, dual PI3K/mTOR inhibitor NVP-BEZ235 to enhance chemotherapy and antiangiogenic response in pancreatic cancer. J Cell Biochem 2012;113:784-91.
23. Alliouachene S, Tuttle RL, Boumard S, Lapointe T, Berissi S, Germain S, et al. Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation. J Clin Invest 2008; 118:3629-38.
24. Meyuhas O, Dreazen A. Ribosomal protein S6 kinase from TOP mRNAs to cell size. Prog Mol Biol Transl Sci 2009;90:109-53.
25. Meyuhas O. Physiological roles of ribosomal protein S6: one of its kind. Int Rev Cell Mol Biol 2008;268:1-37.
26. Ruvinsky I, Sharon N, Lerer T, Cohen H, Stolovich-Rain M, Nir T, et al. Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes Dev 2005;19:2199-211.
27. Panic L, Tamarut S, Sticker-Jantscheff M, Barkic M, Solter D, Uzelac M, et al. Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation. Mol Cell Biol 2006;26:8880-91.
28. Ruvinsky I, Katz M, Dreazen A, Gielchinsky Y, Saada A, Freedman N, et al. Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit. PLoS One 2009;4:e5618.
29. Iwenofu OH, Lackman RD, Staddon AP, Goodwin DG, Haupt HM, Brooks JS. Phospho-S6 ribosomal protein: a potential new predictive sarcoma marker for targeted mTOR therapy. Mod Pathol 2008;21: 231-7.
30. Bellizzi AM, Bloomston M, Zhou XP, Iwenofu OH, Frankel WL. The mTOR pathway is frequently activated in pancreatic ductal adenocarcinoma and chronic pancreatitis. Appl Immunohistochem Mol Morphol 2010;18:442-7.
31. Hsieh AC, Costa M, Zollo O, Davis C, Feldman ME, Testa JR, et al. Genetic dissection of the oncogenicmTORpathway reveals druggable addiction to translational control via 4EBP-eIF4E. Cancer Cell 2010; 17:249-61.
32. Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3p cells are islet progenitors and are distinct from duct progenitors. Development 2002;129:2447-57.
33. Zahr E, Molano RD, Pileggi A, Ichii H, Jose SS, Bocca N, et al. Rapamycin impairs in vivo proliferation of islet beta-cells. Transplantation 2007;84:1576-83.
34. Blando J, Portis M, Benavides F, Alexander A, Mills G, Dave B, et al. PTEN deficiency is fully penetrant for prostate adenocarcinoma in C57BL/6 mice via mTOR-dependent growth. Am J Pathol 2009;174: 1869-79.
35. Yokoyama I, Hayashi S, Kobayashi T, Negita M, Yasutomi M, Uchida K, et al. Immunosuppressive drugs and their effect on experimental tumor growth. Transpl Int 1995;8:251-5.
36. Osvaldt AB, Wendt LR, Bersch VP, Backes AN, de Cassia ASR, Edelweiss MI, et al. Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice. Surgery 2006;140:803-9.
37. Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 2003;4:437-50.
38. Zhu L, Shi G, Schmidt CM, Hruban RH, Konieczny SF. Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am J Pathol 2007;171:263-73.
39. Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science 2008;319:1352-5.
40. Elyada E, Pribluda A, Goldstein RE, Morgenstern Y, Brachya G, Cojocaru G, et al. CKIalpha ablation highlights a critical role for p53 in invasiveness control. Nature 2011;470:409-13.
41. Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, et al. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol 2002;4:993-7.
42. Wang B, Matsuoka S, Carpenter PB, Elledge SJ. 53BP1, a mediator of the DNA damage checkpoint. Science 2002;298:1435-8.
43. Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z. Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants. Cell Cycle 2006;5: 1940-5.
44. Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 2009;136:823-37.
45. Wolpin BM, Hezel AF, Abrams T, Blaszkowsky LS, Meyerhardt JA, Chan JA, et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009;27:193-8.
46. Javle MM, Shroff RT, Xiong H, Varadhachary GA, Fogelman D, Reddy SA, et al. Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC Cancer 2010;10:368.
47. Kennedy AL, Morton JP, Manoharan I, Nelson DM, Jamieson NB, Pawlikowski JS, et al. Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Mol Cell 2011;42:36-49.
48. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, et al. An ATPcompetitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009;284:8023-32.
49. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 2009;7:e38.
50. Choo AY, Yoon SO, Kim SG, Roux PP, Blenis J. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc Natl Acad Sci U S A 2008; 105:17414-9.