The Wnt/β-catenin signaling pathway in liver biology and disease

Expert Review of Gastroenterology and Hepatology

Volumn 4, Issue 6, 2010, Pages 745-756

  Behari, Jaideep ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

ammonia detoxificaiton; bile acid homeostasis; canonical Wnt signaling; cytochrome P450; hepatocellular carcinoma; liver biology; liver fibrosis; metabolic zonation; oxidative stress; Wnt catenin pathway

Indexed keywords

AMMONIA; APC PROTEIN; ASCORBIC ACID; AXIN; BETA CATENIN; CLAUDIN 2; CYTOCHROME P450; GLUTAMATE AMMONIA LIGASE; GLYCOGEN SYNTHASE KINASE 3BETA; HEPATOCYTE NUCLEAR FACTOR 1ALPHA; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; INTERLEUKIN 6; REGUCALCIN; TRANSCRIPTION FACTOR FOXO; WNT PROTEIN;

AMMONIA BLOOD LEVEL; BILE SECRETION; DETOXIFICATION; GENE EXPRESSION; GENE MUTATION; HEPATOBILIARY SYSTEM CANCER; HEPATOBLASTOMA; HUMAN; LIVER ADENOMA; LIVER CANCER; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER DEVELOPMENT; LIVER DISEASE; LIVER FIBROSIS; LIVER FOCAL NODULAR HYPERPLASIA; LIVER METABOLISM; LIVER REGENERATION; NONHUMAN; OXIDATIVE STRESS; POSTNATAL GROWTH; REVIEW; SIGNAL TRANSDUCTION; UREA CYCLE; VITAMIN METABOLISM;

BETA CATENIN; HUMANS; LIVER; LIVER DISEASES; LIVER NEOPLASMS; LIVER REGENERATION; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 78649670044     PISSN: 17474124     EISSN: None     Source Type: Journal    
DOI: 10.1586/egh.10.74     Document Type: Review

References (96)

1. Sharma R P, Chopra VL. Effect of the Wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev. Biol. 48(2), 461-465 (1976).
2. Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31(1), 99-109 (1982).
3. Rijsewijk F, Schuermann M, Wagenaar E et al. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50(4), 649-657 (1987).
4. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell. Dev. Biol. 20, 781-810 (2004).
5. Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J. Biol. Chem. 281(32), 22429-22433 (2006).
6. He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/b-catenin signaling: arrows point the way. Development 131(8), 1663-1677 (2004).
7. MacDonald BT, Tamai K, He X. Wnt/b-catenin signaling: components, mechanisms, and diseases. Dev. Cell. 17(1), 9-26 (2009).
8. Zeng G, Awan F, Otruba W et al. Wnt'er in liver: expression of Wnt and Frizzled genes in mouse. Hepatology 45(1), 195-204 (2007).
9. Panakova D, Sprong H, Marois E, Thiele C, Eaton S. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature 435(7038), 58-65 (2005).
10. Franch-Marro X, Marchand O, Piddini E et al. Glypicans shunt the Wingless signal between local signalling and further transport. Development 132(4), 659-666 (2005).
11. Nelson WJ, Nusse R. Convergence of Wnt, b-catenin, and cadherin pathways. Science 303(5663), 1483-1487 (2004).
12. Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI. a-catenin is a molecular switch that binds E-cadherin-b-catenin and regulates actin-flament assembly. Cell 123(5), 903-915 (2005).
13. Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ. Deconstructing the cadherin-catenin-actin complex. Cell 123(5), 889-901 (2005).
14. Kam Y, Quaranta V. Cadherin-bound b-catenin feeds into the Wnt pathway upon adherens junctions dissociation: evidence for an intersection between b-catenin pools. PLoS ONE 4(2), e4580 (2009).
15. Monga SP, Mars WM, Pediaditakis P et al. Hepatocyte growth factor induces Wnt-independent nuclear translocation of b-catenin after Met-b-catenin dissociation in hepatocytes. Cancer Res. 62(7), 2064-2071 (2002).
16. Zeng G, Apte U, Micsenyi A, Bell A, Monga SP. Tyrosine residues 654 and 670 in b-catenin are crucial in regulation of Met-b-catenin interactions. Exp. Cell. Res. 312(18), 3620-3630 (2006).
17. Semenov MV, Habas R, Macdonald BT, He X. SnapShot: noncanonical Wnt signaling pathways. Cell 131(7), 1378 (2007).
18. Tada M, Kai M. Noncanonical Wnt/PCP signaling during vertebrate gastrulation. Zebrafsh 6(1), 29-40 (2009).
19. Jessen JR. Noncanonical Wnt signaling in tumor progression and metastasis. Zebrafsh 6(1), 21-28 (2009).
20. Wada H, Okamoto H. Roles of noncanonical Wnt/PCP pathway genes in neuronal migration and neurulation in zebrafsh. Zebrafsh 6(1), 3-8 (2009).
21. Nusslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature 287(5785), 795-801 (1980).
22. Nejak-Bowen K, Monga SP. Wnt/b-catenin signaling in hepatic organogenesis. Organogenesis 4(2), 92-99 (2008).
23. Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev. Cell. 18(2), 175-189 (2010).
24. Chu J, Sadler KC. New school in liver development: lessons from zebrafsh. Hepatology 50(5), 1656-1663 (2009).
25. Lemaigre FP. Mechanisms of liver development: concepts for understanding liver disorders and design of novel therapies. Gastroenterology 137(1), 62-79 (2009).
26. Sekine S, Gutierrez PJ, Lan BY, Feng S, Hebrok M. Liver-specifc loss of b-catenin results in delayed hepatocyte proliferation after partial hepatectomy. Hepatology 45(2), 361-368 (2007).
27. Tan X, Behari J, Cieply B, Michalopoulos GK, Monga SP. Conditional deletion of b-catenin reveals its role in liver growth and regeneration. Gastroenterology 131(5), 1561-1572 (2006).
28. Tan X, Apte U, Micsenyi A et al. Epidermal growth factor receptor: a novel target of the Wnt/b-catenin pathway in liver. Gastroenterology 129(1), 285-302 (2005).
29. Nejak-Bowen KN, Thompson MD, Singh S et al. Accelerated liver regeneration and hepatocarcinogenesis in mice over expressing serine-45 mutant b-catenin. Hepatology 51(5), 1603-1613 (2010).
30. Apte U, Singh S, Zeng G et al. b-catenin activation promotes liver regeneration after acetaminophen-induced injury. Am. J. Pathol. 175(3), 1056-1065 (2009).
31. Jungermann K, Katz N. Functional hepatocellular heterogeneity. Hepatology 2(3), 385-395 (1982).
32. Jungermann K, Katz N. Functional specialization of different hepatocyte populations. Physiol. Rev. 69(3), 708-764 (1989).
33. Katz NR. Metabolic heterogeneity of hepatocytes across the liver acinus. J. Nutr. 122(3 Suppl.), 843-849 (1992).
34. Brosnan ME, Brosnan JT. Hepatic glutamate metabolism: a tale of 2 hepatocytes. Am. J. Clin. Nutr. 90(3), 857S-861S (2009).
35. Loeppen S, Schneider D, Gaunitz F et al. Overexpression of glutamine synthetase is associated with b-catenin-mutations in mouse liver tumors during promotion of hepatocarcinogenesis by phenobarbital. Cancer Res. 62(20), 5685-5688 (2002).
36. Nicholes K, Guillet S, Tomlinson E et al. A mouse model of hepatocellular carcinoma: ectopic expression of fbroblast growth factor 19 in skeletal muscle of transgenic mice. Am. J. Pathol. 160(6), 2295-2307 (2002).
37. Benhamouche S, Decaens T, Godard C et al. Apc tumor suppressor gene is the 'zonation-keeper' of mouse liver. Dev. Cell. 10(6), 759-770 (2006).
38. Sekine S, Lan BY, Bedolli M, Feng S, Hebrok M. Liver-specifc loss of b-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice. Hepatology 43(4), 817-825 (2006).
39. Burke ZD, Reed KR, Phesse TJ et al Liver zonation occurs through a b-catenin-dependent, c-Myc-independent mechanism. Gastroenterology 136(7), 2316-2324, e2311-e2313 (2009).
40. Colletti M, Cicchini C, Conigliaro A et al. Convergence of Wnt signaling on the HNF4a-driven transcription in controlling liver zonation. Gastroenterology 137(2), 660-672 (2009).
41. Danielson PB. The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr. Drug Metab. 3(6), 561-597 (2002).
42. Kohle C, Bock KW. Coordinate regulation of human drug-metabolizing enzymes, and conjugate transporters by the Ah receptor, pregnane X receptor and constitutive androstane receptor. Biochem. Pharmacol. 77(4), 689-699 (2009).
43. Loeppen S, Koehle C, Buchmann A, Schwarz M. A b-catenin-dependent pathway regulates expression of cytochrome P450 isoforms in mouse liver tumors. Carcinogenesis 26(1), 239-248 (2005).
44. Gooding PE, Chayen J, Sawyer B, Slater TF. Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration. Chem. Biol. Interact. 20(3), 299-310 (1978).
45. Bühler R, Lindros KO, Nordling A, Johansson I, Ingelman-Sundberg M. Zonation of cytochrome P450 isozyme expression and induction in rat liver. Eur. J. Biochem. 204(1), 407-412 (1992).
46. Hailfnger S, Jaworski M, Braeuning A, Buchmann A, Schwarz M. Zonal gene expression in murine liver: lessons from tumors. Hepatology 43(3), 407-414 (2006).
47. Braeuning A, Sanna R, Huelsken J, Schwarz M. Inducibility of drug-metabolizing enzymes by xenobiotics in mice with liver-specifc knockout of Ctnnb1. Drug Metab. Dispos. 37(5), 1138-1145 (2009).
48. Giera S, Braeuning A, Kohle C et al. Wnt/b-catenin signaling activates and determines hepatic zonal expression of glutathione S-transferases in mouse liver. Toxicol. Sci. 115(1), 22-33 (2010).
49. Gebhardt R. Metabolic zonation of the liver: regulation and implications for liver function. Pharmacol. Ther. 53(3), 275-354 (1992).
50. Audard V, Grimber G, Elie C et al. Cholestasis is a marker for hepatocellular carcinomas displaying b-catenin mutations. J. Pathol. 212(3), 345-352 (2007).
51. Behari J, Yeh TH, Krauland L et al. Liver-specifc b-catenin knockout mice exhibit defective bile acid and cholesterol homeostasis and increased susceptibility to diet-induced steatohepatitis. Am. J. Pathol. 176(2), 744-753 (2010).
52. Yeh TH, Krauland L, Singh V et al. Liver-specifc b-catenin knockout mice have bile canalicular abnormalities, bile secretory defect and intrahepatic cholestasis. Hepatology 52(4), 1410-1419 (2010).
53. Amasheh S, Meiri N, Gitter AH et al. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J. Cell. Science 115(Pt 24), 4969-4976 (2002).
54. Son S, Kojima T, Decaens C et al Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells. Histochem. Cell Biol. 131(3), 411-424 (2009).
55. Theard D, Steiner M, Kalicharan D, Hoekstra D, van Ijzendoorn SC. Cell polarity development and protein traffcking in hepatocytes lacking E-cadherin/b-catenin-based adherens junctions. Mol. Biol. Cell 18(6), 2313-2321 (2007).
56. Nejak-Bowen KN, Zeng G, Tan X, Cieply B, Monga SP. b-catenin regulates vitamin C biosynthesis and cell survival in murine liver. J. Biol. Chem. 284(41), 28115-28127 (2009).
57. Kondo Y, Inai Y, Sato Y et al. Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc. Natl Acad. Sci. USA 103(15), 5723-5728 (2006).
58. Rubinfeld B, Souza B, Albert I et al Association of the APC gene product with b-catenin. Science 262(5140), 1731-1734 (1993).
59. Monga SP. Role of Wnt/b-catenin signaling in liver metabolism and cancer. Int. J. Biochem. Cell. Biol. DOI: 10.1016/j. biocel.2009.09.001 (2009) (Epub ahead of print).
60. Takigawa Y, Brown AM. Wnt signaling in liver cancer. Curr. Drug Targets 9(11), 1013-1024 (2008).
61. Cavard C, Colnot S, Audard V et al Wnt/b-catenin pathway in hepatocellular carcinoma pathogenesis and liver physiology Future Oncol. 4(5), 647-660 (2008).
62. Ihara A, Koizumi H, Hashizume R, Uchikoshi T. Expression of epithelial cadherin and a-and b-catenins in nontumoral livers and hepatocellular carcinomas. Hepatology 23 (6), 1441-1447 (1996).
63. de La Coste A, Romagnolo B, Billuart P et al. Somatic mutations of the b-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc. Natl Acad. Sci. USA 95(15), 8847-8851 (1998).
64. Kondo Y, Kanai Y, Sakamoto M et al. b-catenin accumulation and mutation of exon 3 of the b-catenin gene in hepatocellular carcinoma. Jpn. J. Cancer Res. 90(12), 1301-1309 (1999).
65. Legoix P, Bluteau O, Bayer J et al. b-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity. Oncogene 18(27), 4044-4046 (1999).
66. Wong CM, Fan ST, Ng IO. b-catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic signifcance. Cancer 92(1), 136-145 (2001).
67. Kim M, Lee HC, Tsedensodnom O et al. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/b-catenin signaling pathway in hepatocellular carcinoma cells. J. Hepatol. 48(5), 780-791 (2008).
68. Nhieu JT, Renard CA, Wei Y et al. Nuclear accumulation of mutated b-catenin in hepatocellular carcinoma is associated with increased cell proliferation. Am. J. Pathol. 155(3), 703-710 (1999).
69. Huang H, Fujii H, Sankila A et al. b-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection. Am. J. Pathol. 155(6), 1795-1801 (1999).
70. Laurent-Puig P, Legoix P, Bluteau O et al. Genetic alterations associated with hepatocellular carcinomas defne distinct pathways of hepatocarcinogenesis. Gastroenterology 120(7), 1763-1773 (2001).
71. Cieply B, Zeng G, Proverbs-Singh T, Geller DA, Monga SP. Unique phenotype of hepatocellular cancers with exon-3 mutations in b-catenin gene. Hepatology 49(3), 821-831 (2009).
72. Mao TL, Chu JS, Jeng YM, Lai PL, Hsu HC. Expression of mutant nuclear b-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis. J. Pathol. 193(1), 95-101 (2001).
73. Hsu HC, Jeng YM, Mao TL et al. b-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am. J. Pathol. 157(3), 763-770 (2000).
74. Yuzugullu H, Benhaj K, Ozturk N et al. Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells. Mol. Cancer 8, 90 (2009).
75. Toyama T, Lee HC, Koga H, Wands JR, Kim M. Noncanonical Wnt 11 inhibits hepatocellular carcinoma cell proliferation and migration. Mol. Cancer Res. 8(2), 254-265 (2010).
76. Colnot S, Decaens T, Niwa-Kawakita M et al. Liver-targe ted disruption of APC in mice activates b-catenin signaling and leads to hepatocellular carcinomas. Proc. Natl Acad. Sci. USA 101(49), 17216-17221 (2004).
77. Cadoret A, Ovejero C, Terris B et al. New targets of b-catenin signaling in the liver are involved in the glutamine metabolism. Oncogene 21(54), 8293-8301 (2002).
78. Harada N, Miyoshi H, Murai N et al Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of b-catenin. Cancer Res. 62(7), 1971-1977 (2002).
79. Zhang XF, Tan X, Zeng G et al Conditional b-catenin loss in mice promotes chemical hepatocarcinogenesis: role of oxidative stress and platelet-derived growth factor receptor a/phosphoinositide 3-kinase signaling. Hepatology 52(3), 954-965 (2010).
80. Lucero OM, Dawson DW, Moon RT, Chien AJ. A Re-evaluation of the "oncogenic" nature of Wnt/b-catenin signaling in melanoma and other cancers. Curr. Oncol. Rep. 12(5), 314-318 (2010).
81. Behari J, Zeng G, Otruba W et al R-etodolac decreases b-catenin levels along with survival and proliferation of hepatoma cells. J. Hepatol. 46(5), 849-857 (2007).
82. Koch A, Denkhaus D, Albrecht S et al Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the b-catenin gene. Cancer Res. 59(2), 269-273 (1999).
83. Taniguchi K, Roberts LR, Aderca IN et al Mutational spectrum of b-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene 21(31), 4863-4871 (2002).
84. Wei Y, Fabre M, Branchereau S et al. Activation of b-catenin in epithelial and mesenchymal hepatoblastomas. Oncogene 19(4), 498-504 (2000).
85. Zimmermann A. The emerging family of hepatoblastoma tumours: from ontogenesis to oncogenesis. Eur. J. Cancer 41(11), 1503-1514 (2005).
86. Cairo S, Armengol C, De Reynies A et al Hepatic stem-like phenotype and interplay of Wnt/p-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14(6), 471-484 (2008).
87. Bioulac-Sage P, Rebouissou S, Thomas C et al. Hepatocellular adenoma subtype classifcation using molecular markers and immunohistochemistry. Hepatology 46(3), 740-748 (2007).
88. Rebouissou S, Amessou M, Couchy G et al Frequent in-frame somatic deletions activate gp130 in infammatory hepatocellular tumours. Nature 457(7226), 200-204 (2009).
89. Rebouissou S, Couchy G, Libbrecht L et al The p-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules. J. Hepatol. 49(1), 61-71 (2008)
90. Bioulac-Sage P, Laumonier H, Rullier A et al. Over-expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology. Liver Int. 29(3), 459-465 (2009).
91. Essers MA, de Vries-Smits LM, Barker N et al. Functional interaction between b-catenin and FOXO in oxidative stress signaling. Science 308(5725), 1181-1184 (2005).
92. Funato Y, Michiue T, Asashima M, Miki H. The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-b-catenin signalling through dishevelled. Nat. Cell. Biol. 8(5), 501-508 (2006).
93. Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting b-catenin from T cell factor-to forkhead box O-mediated transcription. J. Biol. Chem. 282(37), 27298-27305 (2007).
94. Jiang F, Parsons CJ, Stefanovic B. Gene expression profle of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation. J. Hepatol. 45(3), 401-409 (2006).
95. Cheng JH, She H, Han YP et al. Wnt antagonism inhibits hepatic stellate cell activation and liver fbrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 294(1), G39-G49 (2008).
96. Gebhardt R, Hovhannisyan A. Organ patterning in the adult stage: the role of Wnt/b-catenin signaling in liver zonation and beyond. Dev. Dyn. 239(1), 45-55 (2010).