Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression

Journal of Clinical Investigation

Volumn 123, Issue 11, 2013, Pages 4681-4694

  Court, Helen ^a   Amoyel, Marc ^a   Hackman, Michael ^a   Lee, Kyoung Eun ^a   Xu, Ruliang ^a   Miller, George ^a   Bar Sagi, Dafna ^a   Bach, Erika A ^a   Bergö, Martin O ^b   Philips, Mark R ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CRE RECOMBINASE; CYCLIN DEPENDENT KINASE INHIBITOR 2A; K RAS PROTEIN; NOTCH RECEPTOR; PROTEIN S ISOPRENYLCYSTEINE O METHYLTRANSFERASE; TRANSCRIPTION FACTOR PDX 1; WNT PROTEIN;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER GROWTH; CARCINOGENESIS; CONTROLLED STUDY; DISEASE EXACERBATION; EPITHELIUM CELL; FEMALE; GENE EXPRESSION; GENE SILENCING; GENOTYPE; HISTOLOGY; HUMAN CELL CULTURE; IMMUNOBLOTTING; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; OSTEOSARCOMA CELL; PANCREAS ADENOCARCINOMA; PANCREAS ADENOMA; PAPILLOMA; PRIORITY JOURNAL; SENESCENCE; WNT SIGNALING PATHWAY;

EID: 84887433950     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI65764     Document Type: Article

References (64)

1. Bos JL. ras oncogenes in human cancer: a review. Cancer Res. 1989;49(17):4682-4689.
2. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3(1):11-22.
3. Vigil D, Cherfils J, Rossman KL, Der CJ. Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer. 2010; 10(12):842-857.
4. Barbacid M. ras genes. Annu Rev Biochem. 1987; 56:779-827.
5. Willumsen BM, Christensen A, Hubbert NL, Papageorge AG, Lowy DR. The p21 ras C-terminus is required for transformation and membrane association. Nature. 1984;310(5978):583-586.
6. Wright LP, Philips MR. Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J Lipid Res. 2006;47(5):883-891.
7. Cox AD, Der CJ. Farnesyltransferase inhibitors: promises and realities. Curr Opin Pharmacol. 2002; 2(4):388-393.
8. Whyte DB, et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem. 1997;272(22):14459- 14464.
9. Bergo MO, et al. Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf. J Clin Invest. 2004;113(4):539-550.
10. Wahlstrom AM, et al. Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease. Blood. 2008;112(4):1357-1365.
11. Hingorani SR, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4(6):437-450.
12. Yonezawa S, Higashi M, Yamada N, Goto M. Precursor lesions of pancreatic cancer. Gut Liver. 2008;2(3):137-154.
13. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53(4):549-554.
14. Shi C, et al. KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin. Mol Cancer Res. 2009;7(2):230-236.
15. Hanlon L, et al. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 2010;70(11):4280- 4286.
16. Mazur PK, et al. Identification of epidermal Pdx1 expression discloses different roles of Notch1 and Notch2 in murine Kras(G12D)-induced skin carcinogenesis in vivo. PLoS One. 2010;5(10):e13578.
17. Maurer-Stroh S, Koranda M, Benetka W, Schneider G, Sirota FL, Eisenhaber F. Towards complete sets of farnesylated and geranylgeranylated proteins. PLoS Comput Biol. 2007;3(4):e66.
18. Ashar HR, et al. Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem. 2000;275(39):30451-30457.
19. Reid TS, Terry KL, Casey PJ, Beese LS. Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Biol. 2004;343(2):417-433.
20. Gannon M, Herrera PL, Wright CV. Mosaic Cremediated recombination in pancreas using the pdx-1 enhancer/promoter. Genesis. 2000;26(2):143-144.
21. Soriano P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet. 1999; 21(1):70-71.
22. Choy E, Philips M. Expression and activity of human prenylcysteine- directed carboxyl methyltransferase. Methods Enzymol. 2000;325:101-114.
23. Hruban RH, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28(8):977-987.
24. Hingorani SR, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7(5):469-483.
25. 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(1):263-273.
26. Chu GC, Kimmelman AC, Hezel AF, DePinho RA. Stromal biology of pancreatic cancer. J Cell Biochem. 2007;101(4):887-907.
27. Bachem MG, et al. Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells. Gastroenterology. 2005;128(4):907-921.
28. Michaelson D, et al. Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases. Mol Biol Cell. 2005; 16(4):1606-1616.
29. Bergo MO, Leung GK, Ambroziak P, Otto JC, Casey PJ, Young SG. Targeted inactivation of the isoprenylcysteine carboxyl methyltransferase gene causes mislocalization of K-Ras in mammalian cells. J Biol Chem. 2000;275(23):17605- 17610.
30. Ijichi H, et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev. 2006;20(22):3147-3160.
31. Guerra C, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11(3):291-302.
32. Lowenfels AB, Maisonneuve P, Lankisch PG. Chronic pancreatitis and other risk factors for pancreatic cancer. Gastroenterol Clin North Am. 1999;28(3):673-685, x.
33. Lampel M, Kern HF. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histol. 1977;373(2):97-117.
34. Watanabe O, Baccino FM, Steer ML, Meldolesi J. Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis. Am J Physiol. 1984; 246(4 pt 1):G457-467.
35. Bedrosian AS, et al. Dendritic cells promote pancreatic viability in mice with acute pancreatitis. Gastroenterology. 2011;141(5):1915-1914.
36. Agbunag C, Lee KE, Buontempo S, Bar-Sagi D. Pancreatic duct epithelial cell isolation and cultivation in two-dimensional and three-dimensional culture systems. Methods Enzymol. 2006;407:703-710.
37. Lee KE, Bar-Sagi D. Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells. Cancer Cell. 2010;18(5):448-458.
38. Nicolas M, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33(3):416-421.
39. Demehri S, Turkoz A, Kopan R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell. 2009;16(1):55-66.
40. Parody TR, Muskavitch MA. The pleiotropic function of Delta during postembryonic development of Drosophila melanogaster. Genetics. 1993;135(2):527-539.
41. Micchelli CA, Rulifson EJ, Blair SS. The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate. Development. 1997;124(8):1485-1495.
42. Radtke F, Raj K. The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer. 2003;3(10):756-767.
43. Ahearn IM, Haigis K, Bar-Sagi D, Philips MR. Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol. 2012;13(1):39-51.
44. Winter-Vann AM, et al. A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells. Proc Natl Acad Sci U S A. 2005;102(12):4336-4341.
45. Judd WR, et al. Discovery and SAR of methylated tetrahydropyranyl derivatives as inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT). J Med Chem. 2011;54(14):5031-5047.
46. Grosshans BL, Ortiz D, Novick P. Rabs and their effectors: achieving specificity in membrane traffic. Proc Natl Acad Sci U S A. 2006;103(32):11821- 11827.
47. Bergo MO, et al. Isoprenylcysteine carboxyl methyltransferase deficiency in mice. J Biol Chem. 2001;276(8):5841-5845.
48. Lin X, Jung J, Kang D, Xu B, Zaret KS, Zoghbi H. Prenylcysteine carboxylmethyltransferase is essential for the earliest stages of liver development in mice. Gastroenterology. 2002;123(1):345-351.
49. Chiu VK, et al. Ras signalling on the endoplasmic reticulum and the Golgi. Nat Cell Biol. 2002;4(5):343-350.
50. Michaelson D, et al. Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases. Mol Biol Cell. 2005; 16(4):1606-1616.
51. Fiordalisi JJ, Holly SP, Johnson RL, Parise LV, Cox AD. A distinct class of dominant negative Ras mutants: cytosolic GTP-bound Ras effector domain mutants that inhibit Ras signaling and transformation and enhance cell adhesion. J Biol Chem. 2002;277(13):10813-10823.
52. Carriere C, Young AL, Gunn JR, Longnecker DS, Korc M. Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras. Biochem Biophys Res Commun. 2009;382(3):561-565.
53. Bardeesy N, et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci U S A. 2006;103(15):5947-5952.
54. Sherr CJ. Principles of tumor suppression. Cell. 2004;116(2):235-246.
55. Mazur PK, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2010;107(30):13438-13443.
56. Le Borgne R, Bardin A, Schweisguth F. The roles of receptor and ligand endocytosis in regulating Notch signaling. Development. 2005;132(8):1751-1762.
57. Jackson EL, et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 2001; 15(24):3243-3248.
58. Olive KP, et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell. 2004;119(6):847-860.
59. Heikkinen S, Argmann CA, Champy MF, Auwerx J. Evaluation of glucose homeostasis. Curr Protoc Mol Biol. 2007;Chapter 29:Unit 29B.3.
60. Hruban RH, Fukushima N. Pancreatic adenocarcinoma: update on the surgical pathology of carcinomas of ductal origin and PanINs. Mod Pathol. 2007;20(suppl 1):S61-S70.
61. Ahearn IM, et al. FKBP12 binds to acylated H-ras and promotes depalmitoylation. Mol Cell. 2011;41(2):173-185.
62. de Rooij J, Bos JL. Minimal Ras-binding domain of Raf1 can be used as an activation-specific probe for Ras. Oncogene. 1997;14(5):623-625.
63. Aste-Amezaga M, et al. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PLoS One. 2010;5(2):e9094.
64. R Development Core Team. R: A Language Environment For Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2012.