Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

Cell Reports

Volumn 14, Issue 10, 2016, Pages 2325-2336

  Liou, Geou Yarh ^a   Döppler, Heike ^a   DelGiorno, Kathleen E ^a,b   Zhang, Lizhi ^c   Leitges, Michael ^d   Crawford, Howard C ^a,e   Murphy, Michael P ^f   Storz, Peter ^a  

^a MAYO CLINIC   (United States)

^b Fred Hutchinson Cancer Research Center   (United States)

^c MAYO CLINIC   (United States)

^d UNIVERSITY OF OSLO   (Norway)

^e UNIVERSITY OF MICHIGAN   (United States)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Growth factor signaling; Kras; Mitochondria; Oxidative stress; Pancreatic cancer; PanIN

Indexed keywords

ADAM PROTEIN; ADAM17 PROTEIN; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; K RAS PROTEIN; LIGAND; MUTANT PROTEIN; NF KAPPA B1; NF KAPPA B2; PROTEIN KINASE; REACTIVE OXYGEN METABOLITE; ROS RECEPTIVE KINASE PROTEIN KINASE D1; UNCLASSIFIED DRUG; EGFR PROTEIN, MOUSE; KRAS2 PROTEIN, MOUSE; PROTEIN KINASE C; PROTEIN KINASE D; PROTEIN P21; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME;

ACINAR CELL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARCINOGENESIS; CELL DEDIFFERENTIATION; CONTROLLED STUDY; DISEASE COURSE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; OXIDATIVE STRESS; PANCREAS CANCER; PANCREAS DISEASE; PANCREATIC PRECANCEROUS LESION; PATHOGENESIS; PHENOTYPE; PRECANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RECEPTOR UPREGULATION; SIGNAL TRANSDUCTION; STEM CELL; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CYTOLOGY; GENETICS; METABOLISM; MITOCHONDRION; PANCREAS TUMOR; PATHOLOGY; RNA INTERFERENCE; SITE DIRECTED MUTAGENESIS; UPREGULATION;

ACINAR CELLS; ADAM17 PROTEIN; ANIMALS; CELLS, CULTURED; EPIDERMAL GROWTH FACTOR; HUMANS; LIGANDS; MICE; MITOCHONDRIA; MUTAGENESIS, SITE-DIRECTED; NF-KAPPA B P52 SUBUNIT; OXIDATIVE STRESS; PANCREATIC NEOPLASMS; PRECANCEROUS CONDITIONS; PROTEIN KINASE C; PROTO-ONCOGENE PROTEINS P21(RAS); REACTIVE OXYGEN SPECIES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RNA INTERFERENCE; SIGNAL TRANSDUCTION; UP-REGULATION;

EID: 84960339672     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.02.029     Document Type: Article

References (43)

1. Ahn C.S., Metallo C.M. Mitochondria as biosynthetic factories for cancer proliferation. Cancer Metab. 2015, 3:1.
2. Al Saati T., Clerc P., Hanoun N., Peuget S., Lulka H., Gigoux V., Capilla F., Béluchon B., Couvelard A., Selves J., et al. Oxidative stress induced by inactivation of TP53INP1 cooperates with KrasG12D to initiate and promote pancreatic carcinogenesis in the murine pancreas. Am. J. Pathol. 2013, 182:1996-2004.
3. Ardito C.M., Grüner B.M., Takeuchi K.K., Lubeseder-Martellato C., Teichmann N., Mazur P.K., Delgiorno K.E., Carpenter E.S., Halbrook C.J., Hall J.C., et al. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell 2012, 22:304-317.
4. 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.
5. Barrera G., Pizzimenti S., Ciamporcero E.S., Daga M., Ullio C., Arcaro A., Cetrangolo G.P., Ferretti C., Dianzani C., Lepore A., Gentile F. Role of 4-hydroxynonenal-protein adducts in human diseases. Antioxid. Redox Signal. 2015, 22:1681-1702.
6. Daniluk J., Liu Y., Deng D., Chu J., Huang H., Gaiser S., Cruz-Monserrate Z., Wang H., Ji B., Logsdon C.D. An NF-κB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice. J. Clin. Invest. 2012, 122:1519-1528.
7. DeNicola G.M., Karreth F.A., Humpton T.J., Gopinathan A., Wei C., Frese K., Mangal D., Yu K.H., Yeo C.J., Calhoun E.S., et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 2011, 475:106-109.
8. Döppler H., Storz P. A novel tyrosine phosphorylation site in protein kinase D contributes to oxidative stress-mediated activation. J. Biol. Chem. 2007, 282:31873-31881.
9. Döppler H., Liou G.Y., Storz P. Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. PLoS ONE 2013, 8:e53676.
10. Gough D.J., Corlett A., Schlessinger K., Wegrzyn J., Larner A.C., Levy D.E. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009, 324:1713-1716.
11. Guerra C., Schuhmacher A.J., Cañamero M., Grippo P.J., Verdaguer L., Pérez-Gallego L., Dubus P., Sandgren E.P., Barbacid M. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 2007, 11:291-302.
12. Hayes J.D., McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 2009, 34:176-188.
13. Hruban R.H., Iacobuzio-Donahue C., Wilentz R.E., Goggins M., Kern S.E. Molecular pathology of pancreatic cancer. Cancer J. 2001, 7:251-258.
14. Hu Y., Lu W., Chen G., Wang P., Chen Z., Zhou Y., Ogasawara M., Trachootham D., Feng L., Pelicano H., et al. K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis. Cell Res. 2012, 22:399-412.
15. Huang H., Daniluk J., Liu Y., Chu J., Li Z., Ji B., Logsdon C.D. Oncogenic K-Ras requires activation for enhanced activity. Oncogene 2014, 33:532-535.
16. Ishikawa K., Takenaga K., Akimoto M., Koshikawa N., Yamaguchi A., Imanishi H., Nakada K., Honma Y., Hayashi J. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 2008, 320:661-664.
17. Jaffee E.M., Hruban R.H., Canto M., Kern S.E. Focus on pancreas cancer. Cancer Cell 2002, 2:25-28.
18. Ji B., Tsou L., Wang H., Gaiser S., Chang D.Z., Daniluk J., Bi Y., Grote T., Longnecker D.S., Logsdon C.D. Ras activity levels control the development of pancreatic diseases. Gastroenterology 2009, 137:1072-1082.
19. Kodydkova J., Vavrova L., Stankova B., Macasek J., Krechler T., Zak A. Antioxidant status and oxidative stress markers in pancreatic cancer and chronic pancreatitis. Pancreas 2013, 42:614-621.
20. Korc M. Role of growth factors in pancreatic cancer. Surg. Oncol. Clin. N. Am. 1998, 7:25-41.
21. Lee A.C., Fenster B.E., Ito H., Takeda K., Bae N.S., Hirai T., Yu Z.X., Ferrans V.J., Howard B.H., Finkel T. Ras proteins induce senescence by altering the intracellular levels of reactive oxygen species. J. Biol. Chem. 1999, 274:7936-7940.
22. Ling J., Kang Y., Zhao R., Xia Q., Lee D.F., Chang Z., Li J., Peng B., Fleming J.B., Wang H., et al. KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012, 21:105-120.
23. Liou G.Y., Storz P. Reactive oxygen species in cancer. Free Radic. Res. 2010, 44:479-496.
24. Liou G.Y., Döppler H., Braun U.B., Panayiotou R., Scotti Buzhardt M., Radisky D.C., Crawford H.C., Fields A.P., Murray N.R., Wang Q.J., et al. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia. Nat. Commun. 2015, 6:6200.
25. Liou G.Y., Döppler H., Necela B., Edenfield B., Zhang L., Dawson D.W., Storz P. Mutant KRAS-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions. Cancer Discov. 2015, 5:52-63.
26. Maniati E., Bossard M., Cook N., Candido J.B., Emami-Shahri N., Nedospasov S.A., Balkwill F.R., Tuveson D.A., Hagemann T. Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. J. Clin. Invest. 2011, 121:4685-4699.
27. Means A.L., Meszoely I.M., Suzuki K., Miyamoto Y., Rustgi A.K., Coffey R.J., Wright C.V., Stoffers D.A., Leach S.D. Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Development 2005, 132:3767-3776.
28. Mishra P.K., Raghuram G.V., Jain D., Jain S.K., Khare N.K., Pathak N. Mitochondrial oxidative stress-induced epigenetic modifications in pancreatic epithelial cells. Int. J. Toxicol. 2014, 33:116-129.
29. Navas C., Hernández-Porras I., Schuhmacher A.J., Sibilia M., Guerra C., Barbacid M. EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma. Cancer Cell 2012, 22:318-330.
30. Pan X., Arumugam T., Yamamoto T., Levin P.A., Ramachandran V., Ji B., Lopez-Berestein G., Vivas-Mejia P.E., Sood A.K., McConkey D.J., Logsdon C.D. Nuclear factor-kappaB p65/relA silencing induces apoptosis and increases gemcitabine effectiveness in a subset of pancreatic cancer cells. Clin. Cancer Res. 2008, 14:8143-8151.
31. Perera R.M., Bardeesy N. Cancer: when antioxidants are bad. Nature 2011, 475:43-44.
32. Sarkisian C.J., Keister B.A., Stairs D.B., Boxer R.B., Moody S.E., Chodosh L.A. Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis. Nat. Cell Biol. 2007, 9:493-505.
33. Shidara Y., Yamagata K., Kanamori T., Nakano K., Kwong J.Q., Manfredi G., Oda H., Ohta S. Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res. 2005, 65:1655-1663.
34. Singh A., Bodas M., Wakabayashi N., Bunz F., Biswal S. Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance. Antioxid. Redox Signal. 2010, 13:1627-1637.
35. Smith R.A., Murphy M.P. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann. N Y Acad. Sci. 2010, 1201:96-103.
36. Son J., Lyssiotis C.A., Ying H., Wang X., Hua S., Ligorio M., Perera R.M., Ferrone C.R., Mullarky E., Shyh-Chang N., et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013, 496:101-105.
37. Storz P., Toker A. Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. EMBO J. 2003, 22:109-120.
38. Storz P., Döppler H., Toker A. Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Mol. Cell. Biol. 2005, 25:8520-8530.
39. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033.
40. Weinberg F., Hamanaka R., Wheaton W.W., Weinberg S., Joseph J., Lopez M., Kalyanaraman B., Mutlu G.M., Budinger G.R., Chandel N.S. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl. Acad. Sci. USA 2010, 107:8788-8793.
41. Zhang J., Johnston G., Stebler B., Keller E.T. Hydrogen peroxide activates NFkappaB and the interleukin-6 promoter through NFkappaB-inducing kinase. Antioxid. Redox Signal. 2001, 3:493-504.
42. Zhang P., Singh A., Yegnasubramanian S., Esopi D., Kombairaju P., Bodas M., Wu H., Bova S.G., Biswal S. Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol. Cancer Ther. 2010, 9:336-346.
43. Zheng H., Shen M., Zha Y.L., Li W., Wei Y., Blanco M.A., Ren G., Zhou T., Storz P., Wang H.Y., Kang Y. PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis. Cancer Cell 2014, 26:358-373.