KrasG12D-Induced IKK2/β/NF-κB Activation by IL-1α and p62 Feedforward Loops Is Required for Development of Pancreatic Ductal Adenocarcinoma

Cancer Cell

Volumn 21, Issue 1, 2012, Pages 105-120

  Ling, Jianhua ^a   Kang, Ya'an ^a   Zhao, Ruiying ^a   Xia, Qianghua ^a,b   Lee, Dung Fang ^c   Chang, Zhe ^a,b   Li, Jin ^d   Peng, Bailu ^e   Fleming, Jason B ^a   Wang, Huamin ^a,b   Liu, Jinsong ^a,b   Lemischka, Ihor R ^c   Hung, Mien Chie ^a,b,f   Chiao, PaulJ ^a,b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF TEXAS   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^d CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^e Guangdong Academy of Sciences   (China)

^f CHINA MEDICAL UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

I KAPPA B KINASE BETA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1ALPHA; K RAS PROTEIN; PROTEIN P62; CYTOKINE; I KAPPA B KINASE; IKK2 PROTEIN, MOUSE; KRAS PROTEIN, HUMAN; KRAS2 PROTEIN, MOUSE; ONCOPROTEIN; PROTEIN P21; RAS PROTEIN; SIGNAL TRANSDUCING ADAPTOR PROTEIN; SQSTM1 PROTEIN, HUMAN; TRANSCRIPTION FACTOR AP 1;

ANIMAL EXPERIMENT; ARTICLE; CANCER SURVIVAL; CARCINOGENESIS; CONTROLLED STUDY; CORRELATION ANALYSIS; DOWN REGULATION; ENZYME ACTIVATION; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; GENE SILENCING; GENETIC ASSOCIATION; HUMAN; MOUSE; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREATIC DUCTAL ADENOCARCINOMA; PRIORITY JOURNAL; ANIMAL; CELL PROLIFERATION; DRUG ANTAGONISM; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MUTATION; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

MUS;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CELL PROLIFERATION; CYTOKINES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; I-KAPPA B KINASE; INTERLEUKIN-1ALPHA; MICE; MUTATION; NF-KAPPA B; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS P21(RAS); RAS PROTEINS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR AP-1;

EID: 84855946746     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2011.12.006     Document Type: Article

References (42)

1. Aguirre A.J., Bardeesy N., Sinha M., Lopez L., Tuveson D.A., Horner J., Redston M.S., DePinho R.A. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 2003, 17:3112-3126.
2. Barbie D.A., Tamayo P., Boehm J.S., Kim S.Y., Moody S.E., Dunn I.F., Schinzel A.C., Sandy P., Meylan E., Scholl C., et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 2009, 462:108-112.
3. Bardeesy N., Aguirre A.J., Chu G.C., Cheng K.H., Lopez L.V., Hezel A.F., Feng B., Brennan C., Weissleder R., Mahmood U., et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc. Natl. Acad. Sci. USA 2006, 103:5947-5952.
4. Bassères D.S., Ebbs A., Levantini E., Baldwin A.S. Requirement of the NF-kappaB subunit p65/RelA for K-Ras-induced lung tumorigenesis. Cancer Res. 2010, 70:3537-3546.
5. Brentnall T.A., Bronner M.P., Byrd D.R., Haggitt R.C., Kimmey M.B. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann. Intern. Med. 1999, 131:247-255.
6. Chien Y., Kim S., Bumeister R., Loo Y.M., Kwon S.W., Johnson C.L., Balakireva M.G., Romeo Y., Kopelovich L., Gale M., et al. RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell 2006, 127:157-170.
7. Dajee M., Lazarov M., Zhang J.Y., Cai T., Green C.L., Russell A.J., Marinkovich M.P., Tao S., Lin Q., Kubo Y., Khavari P.A. NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 2003, 421:639-643.
8. Duran A., Linares J.F., Galvez A.S., Wikenheiser K., Flores J.M., Diaz-Meco M.T., Moscat J. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 2008, 13:343-354.
9. Fujioka S., Sclabas G.M., Schmidt C., Niu J., Frederick W.A., Dong Q.G., Abbruzzese J.L., Evans D.B., Baker C., Chiao P.J. Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis. Oncogene 2003, 22:1365-1370.
10. Gabay C., Lamacchia C., Palmer G. IL-1 pathways in inflammation and human diseases. Nat. Rev. Rheumatol. 2010, 6:232-241.
11. Greten F.R., Arkan M.C., Bollrath J., Hsu L.C., Goode J., Miething C., Göktuna S.I., Neuenhahn M., Fierer J., Paxian S., et al. NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell 2007, 130:918-931.
12. Gu G., Dubauskaite J., Melton D.A. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002, 129:2447-2457.
13. He G., Yu G.Y., Temkin V., Ogata H., Kuntzen C., Sakurai T., Sieghart W., Peck-Radosavljevic M., Leffert H.L., Karin M. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 2010, 17:286-297.
14. Hingorani S.R., Petricoin E.F., Maitra A., Rajapakse V., King C., Jacobetz M.A., Ross S., Conrads T.P., Veenstra T.D., Hitt B.A., et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 2003, 4:437-450.
15. Hruban R.H., Goggins M., Parsons J., Kern S.E. Progression model for pancreatic cancer. Clin. Cancer Res. 2000, 6:2969-2972.
16. Hu M.C., Lee D.F., Xia W., Golfman L.S., Ou-Yang F., Yang J.Y., Zou Y., Bao S., Hanada N., Saso H., et al. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 2004, 117:225-237.
17. Johnson L., Mercer K., Greenbaum D., Bronson R.T., Crowley D., Tuveson D.A., Jacks T. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 2001, 410:1111-1116.
18. Karin M. The IkappaB kinase - a bridge between inflammation and cancer. Cell Res. 2008, 18:334-342.
19. Kim M.P., Evans D.B., Wang H., Abbruzzese J.L., Fleming J.B., Gallick G.E. Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice. Nat. Protoc. 2009, 4:1670-1680.
20. Lee D.F., Kuo H.P., Chen C.T., Hsu J.M., Chou C.K., Wei Y., Sun H.L., Li L.Y., Ping B., Huang W.C., et al. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell 2007, 130:440-455.
21. Lee K.M., Yasuda H., Hollingsworth M.A., Ouellette M.M. Notch 2-positive progenitors with the intrinsic ability to give rise to pancreatic ductal cells. Lab. Invest. 2005, 85:1003-1012.
22. Li Z.W., Omori S.A., Labuda T., Karin M., Rickert R.C. IKK beta is required for peripheral B cell survival and proliferation. J.Immunol. 2003, 170:4630-4637.
23. Lomaga M.A., Yeh W.C., Sarosi I., Duncan G.S., Furlonger C., Ho A., Morony S., Capparelli C., Van G., Kaufman S., et al. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 1999, 13:1015-1024.
24. Lowenfels A.B., Maisonneuve P., DiMagno E.P., Elitsur Y., Gates L.K., Perrault J., Whitcomb D.C. Hereditary pancreatitis and the risk of pancreatic cancer. J.Natl. Cancer Inst. 1997, 89:442-446. International Hereditary Pancreatitis Study Group.
25. Maeda S., Kamata H., Luo J.L., Leffert H., Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005, 121:977-990.
26. Meylan E., Dooley A.L., Feldser D.M., Shen L., Turk E., Ouyang C., Jacks T. Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 2009, 462:104-107.
27. Mori N., Prager D. Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins. Blood 1996, 87:3410-3417.
28. Naito A., Azuma S., Tanaka S., Miyazaki T., Takaki S., Takatsu K., Nakao K., Nakamura K., Katsuki M., Yamamoto T., Inoue J. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 1999, 4:353-362.
29. Osborn L., Kunkel S., Nabel G.J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc. Natl. Acad. Sci. USA 1989, 86:2336-2340.
30. Peng B., Ling J., Lee A.J., Wang Z., Chang Z., Jin W., Kang Y., Zhang R., Shim D., Wang H., et al. Defective feedback regulation of NF-kappaB underlies Sjogren's syndrome in mice with mutated kappaB enhancers of the IkappaBalpha promoter. Proc. Natl. Acad. Sci. USA 2010, 107:15193-15198.
31. Pomerantz J.L., Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 1999, 18:6694-6704.
32. Qian J., Niu J., Li M., Chiao P.J., Tsao M.S. Invitro modeling of human pancreatic duct epithelial cell transformation defines gene expression changes induced by K-ras oncogenic activation in pancreatic carcinogenesis. Cancer Res. 2005, 65:5045-5053.
33. Sanz L., Diaz-Meco M.T., Nakano H., Moscat J. The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway. EMBO J. 2000, 19:1576-1586.
34. Skaug B., Jiang X., Chen Z.J. The role of ubiquitin in NF-kappaB regulatory pathways. Annu. Rev. Biochem. 2009, 78:769-796.
35. Staudt L.M. Oncogenic activation of NF-kappaB. Cold Spring Harb. Perspect. Biol. 2010, 2:a000109.
36. Tuveson D.A., Shaw A.T., Willis N.A., Silver D.P., Jackson E.L., Chang S., Mercer K.L., Grochow R., Hock H., Crowley D., et al. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 2004, 5:375-387.
37. Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., Chen Z.J. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 2001, 412:346-351.
38. Wang W., Abbruzzese J.L., Evans D.B., Larry L., Cleary K.R., Chiao P.J. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin. Cancer Res. 1999, 5:119-127.
39. Wislez M., Spencer M.L., Izzo J.G., Juroske D.M., Balhara K., Cody D.D., Price R.E., Hittelman W.N., Wistuba I.I., Kurie J.M. Inhibition of mammalian target of rapamycin reverses alveolar epithelial neoplasia induced by oncogenic K-ras. Cancer Res. 2005, 65:3226-3235.
40. Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T., Moscat J. The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J.Biol. Chem. 2005, 280:35625-35629.
41. Yang J., Splittgerber R., Yull F.E., Kantrow S., Ayers G.D., Karin M., Richmond A. Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J.Clin. Invest. 2010, 120:2563-2574.
42. Zabel U., Henkel T., Silva M.S., Baeuerle P.A. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus. EMBO J. 1993, 12:201-211.