Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis

Nature Communications

Volumn 8, Issue , 2017, Pages

  Zhou, Mei ^a   Yang, Hong ^a   Learned, R Marc ^a   Tian, Hui ^a   Ling, Lei ^a  

^a NGM Biopharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; FIBROBLAST GROWTH FACTOR 19; GLUCOSE; INTERLEUKIN 6; INTERLEUKIN 6 ANTIBODY; JANUS KINASE INHIBITOR; NEUTRALIZING ANTIBODY; STAT3 PROTEIN; FGF19 PROTEIN, HUMAN; FIBROBLAST GROWTH FACTOR; IL6 PROTEIN, HUMAN; INTERLEUKIN-6, MOUSE; STAT3 PROTEIN, HUMAN; STAT3 PROTEIN, MOUSE;

ANTIBODY; CANCER; GENE EXPRESSION; GENETIC VARIATION; GLUCOSE; INHIBITOR; METABOLISM; MORTALITY; RODENT; TUMOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE ACID METABOLISM; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENERGY METABOLISM; GENE DELETION; GLUCOSE METABOLISM; HUMAN; HUMAN TISSUE; LIVER CARCINOGENESIS; LIVER CELL; LIVER CELL CARCINOMA; MALE; MOUSE; NONHUMAN; SIGNAL TRANSDUCTION; ANIMAL; BIOLOGY; BODY COMPOSITION; CHEMISTRY; DEPENDOPARVOVIRUS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; HEK293 CELL LINE; LIVER TUMOR; METABOLISM; TRANSGENE;

MUS;

ANIMALS; BILE ACIDS AND SALTS; BODY COMPOSITION; CARCINOMA, HEPATOCELLULAR; COMPUTATIONAL BIOLOGY; DEPENDOVIRUS; ENERGY METABOLISM; FEMALE; FIBROBLAST GROWTH FACTORS; GENE DELETION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE; HEK293 CELLS; HUMANS; INTERLEUKIN-6; LIVER NEOPLASMS; MALE; MICE; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TRANSGENES;

EID: 85019480553     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms15433     Document Type: Article

References (62)

1. Llovet, J. M., et al. Hepatocellular carcinoma. Nat. Rev. Dis. Primers 2, 16018 (2016).
2. El-Serag, H. B. Hepatocellular carcinoma. N. Engl. J. Med. 365, 1118-1127 (2011).
3. Sun, B., Karin, M. Obesity, inflammation, and liver cancer. J. Hepatol. 56, 704-713 (2012).
4. Michelotti, G. A., Machado, M. V., Diehl, A. M. NAFLD, NASH and liver cancer. Nat. Rev. Gastroenterol. Hepatol. 10, 656-665 (2013).
5. Zucman-Rossi, J., Villanueva, A., Nault, J. C., Llovet, J. M. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149, 1226-1239 e1224 (2015).
6. Sawey, E. T., et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening. Cancer Cell 19, 347-358 (2011).
7. Ahn, S. M., et al. Genomic portrait of resectable hepatocellular carcinomas: Implications of RB1 and FGF19 aberrations for patient stratification. Hepatology 60, 1972-1982 (2014).
8. Hyeon, J., Ahn, S., Lee, J. J., Song, D. H., Park, C. K. Expression of fibroblast growth factor 19 is associated with recurrence and poor prognosis of hepatocellular carcinoma. Diges. Dis. Sci. 58, 1916-1922 (2013).
9. Miura, S., et al. Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma. BMC Cancer 12, 56 (2012).
10. Schulze, K., et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat. Genet. 47, 505-511 (2015).
11. Nicholes, K., et al. A mouse model of hepatocellular carcinoma: Ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice. Am. J. Pathol. 160, 2295-2307 (2002).
12. Zhou, M., et al. Separating tumorigenicity from bile acid regulatory activity for endocrine hormone FGF19. Cancer Res. 74, 3306-3316 (2014).
13. Kliewer, S. A., Mangelsdorf, D. J. Bile acids as hormones: The FXR-FGF15/19 pathway. Digestive Dis. 33, 327-331 (2015).
14. Degirolamo, C., Sabba, C., Moschetta, A. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nat. Rev. Drug Discov. 15, 51-69 (2016).
15. French, D. M., et al. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models. PLoS ONE 7, e36713 (2012).
16. Desnoyers, L. R., et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene 27, 85-97 (2008).
17. Pai, R., et al. Antibody-mediated inhibition of fibroblast growth factor 19 results in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys. Toxicol. Sci.: Off. J. Soc. Toxicol. 126, 446-456 (2012).
18. Hagel, M., et al. First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular carcinomas with an activated fgfr4 signaling pathway. Cancer Discov. 5, 424-437 (2015).
19. Bromberg, J. F., et al. Stat3 as an oncogene. Cell 98, 295-303 (1999).
20. Yu, H., Pardoll, D., Jove, R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat. Rev. Cancer 9, 798-809 (2009).
21. Yu, H., Lee, H., Herrmann, A., Buettner, R., Jove, R. Revisiting STAT3 signalling in cancer: New and unexpected biological functions. Nat. Rev. Cancer 14, 736-746 (2014).
22. Carrillo-Carrasco, N., Chandler, R. J., Chandrasekaran, S., Venditti, C. P. Liver-directed recombinant adeno-associated viral gene delivery rescues a lethal mouse model of methylmalonic acidemia and provides long-term phenotypic correction. Hum. Gene Therapy 21, 1147-1154 (2010).
23. Moh, A., et al. Role of STAT3 in liver regeneration: Survival, DNA synthesis, inflammatory reaction and liver mass recovery. Lab. Investig.; J. Tech. Methods Pathol. 87, 1018-1028 (2007).
24. Marrero, J. A., El-Serag, H. B. Alpha-fetoprotein should be included in the hepatocellular carcinoma surveillance guidelines of the American Association for the Study of Liver Diseases. Hepatology 53, 1060-1062 (2011).
25. Potthoff, M. J., et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1alpha pathway. Cell Metab. 13, 729-738 (2011).
26. Tomlinson, E., et al. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity. Endocrinology 143, 1741-1747 (2002).
27. Morton, G. J., et al. FGF19 action in the brain induces insulin-independent glucose lowering. J. Clin. Investig. 123, 4799-4808 (2013).
28. Perry, R. J., et al. FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nat. Commun. 6, 6980 (2015).
29. Kir, S., et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 331, 1621-1624 (2011).
30. Taga, T. Gp130, a shared signal transducing receptor component for hematopoietic and neuropoietic cytokines. J. Neurochem. 67, 1-10 (1996).
31. Zhong, Z., Wen, Z., Darnell, J. E. Jr. Stat3: A STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264, 95-98 (1994).
32. Weber-Nordt, R. M., et al. Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain. J. Biol. Chem. 271, 27954-27961 (1996).
33. Brenne, A. T., et al. Interleukin-21 is a growth and survival factor for human myeloma cells. Blood 99, 3756-3762 (2002).
34. Radaeva, S., Sun, R., Pan, H. N., Hong, F., Gao, B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39, 1332-1342 (2004).
35. Chattopadhyay, S., et al. Interleukin-31 and oncostatin-M mediate distinct signaling reactions and response patterns in lung epithelial cells. J. Biol. Chem. 282, 3014-3026 (2007).
36. Wunderlich, F. T., et al. Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. Cell Metab. 12, 237-249 (2010).
37. Zhou, M., et al. Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2-deficient mice. Hepatology 63, 914-929 (2016).
38. El-Serag, H. B. Hepatocellular carcinoma: Recent trends in the United States. Gastroenterology 127, S27-S34 (2004).
39. Kishimoto, T. Interleukin-6: From basic science to medicine-40 years in immunology. Annu. Rev. Immunol. 23, 1-21 (2005).
40. Guschin, D., et al. A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 14, 1421-1429 (1995).
41. Fleischmann, R., et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl. J. Med. 367, 495-507 (2012).
42. van Rhee, F., et al. Siltuximab for multicentric Castleman's disease: A randomised, double-blind, placebo-controlled trial. Lancet Oncol. 15, 966-974 (2014).
43. Smolen, J. S., et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): A double-blind, placebocontrolled, randomised trial. Lancet 371, 987-997 (2008).
44. He, G., et al. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 17, 286-297 (2010).
45. Bard-Chapeau, E. A., et al. Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell 19, 629-639 (2011).
46. Porta, C., et al. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann. Oncol.: Off. J. Eur. Soc. Med. Oncol. 19, 353-358 (2008).
47. Chun, Y. S., Calderaro, J., Zucman-Rossi, J. Synchronous hepatocellular carcinoma and Castleman's disease: The role of the interleukin-6-signaling pathway. Hepatology 56, 392-393 (2012).
48. Maione, D., et al. Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. EMBO J. 17, 5588-5597 (1998).
49. He, G., et al. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 155, 384-396 (2013).
50. Wan, S., et al. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology 147, 1393-1404 (2014).
51. Lee, T. K., et al. CD24(\+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 9, 50-63 (2011).
52. Yang, Z. F., et al. Significance of CD90\+ cancer stem cells in human liver cancer. Cancer Cell 13, 153-166 (2008).
53. Ma, S., et al. miR-130b Promotes CD133(\+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell 7, 694-707 (2010).
54. Yamashita, T., et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 136, 1012-1024 (2009).
55. Schaap, F. G., van der Gaag, N. A., Gouma, D. J., Jansen, P. L. High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis. Hepatology 49, 1228-1235 (2009).
56. Pai, R., et al. Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating beta-catenin signaling. Cancer Res. 68, 5086-5095 (2008).
57. Latasa, M. U., et al. Regulation of amphiregulin gene expression by beta-catenin signaling in human hepatocellular carcinoma cells: A novel crosstalk between FGF19 and the EGFR system. PLoS ONE 7, e52711 (2012).
58. Eswarakumar, V. P., Lax, I., Schlessinger, J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 16, 139-149 (2005).
59. Dienstmann, R., et al. Genomic aberrations in the FGFR pathway: Opportunities for targeted therapies in solid tumors. Ann. Oncol.: Off. J. Eur. Soc. Med. Oncol. 25, 552-563 (2014).
60. Ulaganathan, V. K., Sperl, B., Rapp, U. R., Ullrich, A. Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding site. Nature 528, 570-574 (2015).
61. Naugler, W. E., et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317, 121-124 (2007).
62. Park, E. J., et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140, 197-208 (2010).