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Cited by 260Wnt/β-catenin signaling in development and cancerLiver physiology and pathologyHepatocellular Carcinoma Treatment and Prognosis

Beta-catenin signaling, liver regeneration and hepatocellular cancer: sorting the good from the bad

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Nejak-Bowen, Kari Nichole, Monga, Satdarshan P.S.·2011·Seminars in Cancer Biology
DOI 10.1016/j.semcancer.2010.12.010PMC PMC3050081
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Abstract

Among the adult organs, liver is unique for its ability to regenerate. A concerted signaling cascade enables optimum initiation of the regeneration process following insults brought about by surgery or a toxicant. Additionally, there exists a cellular redundancy, whereby a transiently amplifying progenitor population appears and expands to ensure regeneration, when differentiated cells of the liver are unable to proliferate in both experimental and clinical scenarios. One such pathway of relevance in these phenomena is Wnt/β-catenin signaling, which is activated relatively early during regeneration mostly through post-translational modifications. Once activated, β-catenin signaling drives the expression of target genes that are critical for cell cycle progression and contribute to initiation of the regeneration process. The role and regulation of Wnt/β-catenin signaling is now documented in rats, mice, zebrafish and patients. More recently, a regenerative advantage of the livers in β-catenin overexpressing mice was reported, as was also the case after exogenous Wnt-1 delivery to the liver paving the way for assessing means to stimulate the pathway for therapeutics in liver failure. β-Catenin is also pertinent in hepatic oval cell activation and differentiation. However, aberrant activation of the Wnt/β-catenin signaling is reported in a significant subset of hepatocellular cancers (HCC). While many mechanisms of such activation have been reported, the most functional means of aberrant and sustained activation is through mutations in the β-catenin gene or in AXIN1/2, which encodes for a scaffolding protein critical for β-catenin degradation. Intriguingly, in experimental models hepatic overexpression of normal or mutant β-catenin is insufficient for tumorigenesis. In fact β-catenin loss promoted chemical carcinogenesis in the liver due to alternate mechanisms. Since most HCC occur in the backdrop of chronic hepatic injury, where hepatic regeneration is necessary for maintenance of liver function, but at the same time serves as the basis of dysplastic changes, this Promethean attribute exhibits a Jekyll and Hyde behavior that makes distinguishing good regeneration from bad regeneration essential for targeting selective molecular pathways as personalized medicine becomes a norm in clinical practice. Could β-catenin signaling be one such pathway that may be redundant in regeneration and indispensible in HCC in a subset of cases?

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  • No detailed characterization of underlying mechanisms of Wnt-signaling molecular classes in HCC has been pursued yet.

    “Although several molecular classes have been associated with Wnt-signaling in HCC (5, 6, 8) and the concept of liver-related and classical Wnt-signaling has been proposed (29), no detailed characterization of underlying mechanisms has been pursued yet.”

    From Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib (2012) · cites this paper as [29]

    In ‘Phenotype of β-catenin-active HCC’ (page unavailable), the review says important questions about different modes of β-catenin activation remain unanswered and calls for careful comparative analysis. But ‘Activation of Wnt signaling in HCC in patients’ describes several underlying mechanisms already reported. The claim that no detailed characterization has been pursued is therefore broader than the review supports. (LLM, conf=0.82)

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  1. [1]Wodarz A Nusse R Mechanisms of Wnt signaling in development Annual review of cell and developmental biology 1998 14 59 88 9891778
  2. [2]Cadigan KM Nusse R Wnt signaling: a common theme in animal development Genes Dev 1997 11 3286 305 9407023
  3. [3]Nusse R Wnt signaling in disease and in development Cell Res 2005 15 28 32 15686623
  4. [4]Logan CY Nusse R The Wnt signaling pathway in development and disease Annual review of cell and developmental biology 2004 20 781 810 15473860
  5. [5]Peifer M Polakis P Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus Science (New York, NY) 2000 287 1606 9 10733430
  6. [7]Thompson MD Monga SP WNT/beta-catenin signaling in liver health and disease Hepatology 2007 45 1298 305 17464972
  7. [8]Clevers H Wnt/beta-catenin signaling in development and disease Cell 2006 127 469 80 17081971
  8. [9]Wong HC Bourdelas A Krauss A Lee HJ Shao Y Wu D Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled Mol Cell 2003 12 1251 60 14636582 PMC4381837
  9. [10]Cliffe A Hamada F Bienz M A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling Curr Biol 2003 13 960 6 12781135
  10. [12]Zeng X Tamai K Doble B Li S Huang H Habas R A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation Nature 2005 438 873 7 16341017 PMC2100418
  11. [13]Cadigan KM Liu YI Wnt signaling: complexity at the surface J Cell Sci 2006 119 395 402 16443747
  12. [14]Yokoya F Imamoto N Tachibana T Yoneda Y beta-catenin can be transported into the nucleus in a Ran-unassisted manner Mol Biol Cell 1999 10 1119 31 10198061 PMC25239
  13. [15]Huber O Korn R McLaughlin J Ohsugi M Herrmann BG Kemler R Nuclear localization of beta-catenin by interaction with transcription factor LEF-1 Mech Dev 1996 59 3 10 8892228
  14. [16]Zeng G Awan F Otruba W Muller P Apte U Tan X Wnt’er in liver: expression of Wnt and frizzled genes in mouse Hepatology 2007 45 195 204 17187422
  15. [17]Decaens T Godard C de Reynies A Rickman DS Tronche F Couty JP Stabilization of beta-catenin affects mouse embryonic liver growth and hepatoblast fate Hepatology 2008 47 247 58 18038450
  16. [18]Hussain SZ Sneddon T Tan X Micsenyi A Michalopoulos GK Monga SP Wnt impacts growth and differentiation in ex vivo liver development Exp Cell Res 2004 292 157 69 14720515
  17. [19]Monga SP Monga HK Tan X Mule K Pediaditakis P Michalopoulos GK Beta-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification Gastroenterology 2003 124 202 16 12512043
  18. [20]Thompson MD Awuah P Singh S Monga SP Disparate cellular basis of improved liver repair in beta-catenin-overexpressing mice after long-term exposure to 3,5-diethoxycarbonyl-1,4-dihydrocollidine Am J Pathol 2010 177 1812 22 20813968 PMC2947277
  19. [21]Klein D Demory A Peyre F Kroll J Augustin HG Helfrich W Wnt2 acts as a cell type-specific, autocrine growth factor in rat hepatic sinusoidal endothelial cells cross-stimulating the VEGF pathway Hepatology 2008 47 1018 31 18302287
  20. [22]Kordes C Sawitza I Haussinger D Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells Biochem Biophys Res Commun 2008 367 116 23 18158920
  21. [23]Cheng JH She H Han YP Wang J Xiong S Asahina K Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis Am J Physiol Gastrointest Liver Physiol 2008 294 G39 49 18006602
  22. [24]Jiang F Parsons CJ Stefanovic B Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation Journal of hepatology 2006 45 401 9 16780995
  23. [25]Benhamouche S Decaens T Godard C Chambrey R Rickman DS Moinard C Apc tumor suppressor gene is the “zonation-keeper” of mouse liver Dev Cell 2006 10 759 70 16740478
  24. [26]Braeuning A Menzel M Kleinschnitz EM Harada N Tamai Y Kohle C Serum components and activated Ha-ras antagonize expression of perivenous marker genes stimulated by beta-catenin signaling in mouse hepatocytes FEBS J 2007 274 4766 77 17697114
  25. [27]Colletti M Cicchini C Conigliaro A Santangelo L Alonzi T Pasquini E Convergence of Wnt signaling on the HNF4alpha-driven transcription in controlling liver zonation Gastroenterology 2009 137 660 72 19454287
  26. [28]Lilien J Balsamo J The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin Curr Opin Cell Biol 2005 17 459 65 16099633
  27. [29]Orsulic S Huber O Aberle H Arnold S Kemler R E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation J Cell Sci 1999 112 Pt 8 1237 45 10085258
  28. [30]Aberle H Butz S Stappert J Weissig H Kemler R Hoschuetzky H Assembly of the cadherin-catenin complex in vitro with recombinant proteins J Cell Sci 1994 107 Pt 12 3655 63 7706414
  29. [31]Piedra J Martinez D Castano J Miravet S Dunach M de Herreros AG Regulation of beta-catenin structure and activity by tyrosine phosphorylation J Biol Chem 2001 276 20436 43 11279024
  30. [32]Roura S Miravet S Piedra J Garcia de Herreros A Dunach M Regulation of E-cadherin/Catenin association by tyrosine phosphorylation J Biol Chem 1999 274 36734 40 10593980
  31. [33]Theard D Steiner M Kalicharan D Hoekstra D van Ijzendoorn SC Cell polarity development and protein trafficking in hepatocytes lacking E-cadherin/beta-catenin-based adherens junctions Mol Biol Cell 2007 18 2313 21 17429067 PMC1877101
  32. [34]Gumbiner BM Regulation of cadherin-mediated adhesion in morphogenesis Nature reviews 2005 6 622 34 16025097
  33. [35]Zarnegar R Regulation of HGF and HGFR gene expression Exs 1995 74 33 49 8527900
  34. [36]Monga SP Mars WM Pediaditakis P Bell A Mule K Bowen WC Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes Cancer research 2002 62 2064 71 11929826
  35. [37]Papkoff J Aikawa M WNT-1 and HGF regulate GSK3 beta activity and beta-catenin signaling in mammary epithelial cells Biochem Biophys Res Commun 1998 247 851 8 9647782
  36. [38]Zeng G Apte U Micsenyi A Bell A Monga SP Tyrosine residues 654 and 670 in beta-catenin are crucial in regulation of Met-beta-catenin interactions Exp Cell Res 2006 312 3620 30 16952352 PMC1820835
  37. [39]Ishibe S Haydu JE Togawa A Marlier A Cantley LG Cell confluence regulates hepatocyte growth factor-stimulated cell morphogenesis in a beta-catenin-dependent manner Mol Cell Biol 2006 26 9232 43 17030602 PMC1698536
  38. [40]Monga SP Micsenyi A Germinaro M Apte U Bell A beta-Catenin regulation during matrigel-induced rat hepatocyte differentiation Cell Tissue Res 2006 323 71 9 16160859
  39. [41]Shibamoto S Hayakawa M Takeuchi K Hori T Oku N Miyazawa K Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells Cell adhesion and communication 1994 1 295 305 8081883
  40. [42]Apte U Zeng G Muller P Tan X Micsenyi A Cieply B Activation of Wnt/beta-catenin pathway during hepatocyte growth factor-induced hepatomegaly in mice Hepatology 2006 44 992 1002 17006939
  41. [43]Patil MA Lee SA Macias E Lam ET Xu C Jones KD Role of cyclin D1 as a mediator of c-Met-and beta-catenin-induced hepatocarcinogenesis Cancer research 2009 69 253 61 19118010 PMC2628201
  42. [44]Tward AD Jones KD Yant S Cheung ST Fan ST Chen X Distinct pathways of genomic progression to benign and malignant tumors of the liver Proc Natl Acad Sci U S A 2007 104 14771 6 17785413 PMC1964540
  43. [45]Shibata T Ochiai A Kanai Y Akimoto S Gotoh M Yasui N Dominant negative inhibition of the association between beta-catenin and c-erbB-2 by N-terminally deleted beta-catenin suppresses the invasion and metastasis of cancer cells Oncogene 1996 13 883 9 8806677
  44. [46]Bonvini P An WG Rosolen A Nguyen P Trepel J Garcia de Herreros A Geldanamycin abrogates ErbB2 association with proteasome-resistant beta-catenin in melanoma cells, increases beta-catenin-E-cadherin association, and decreases beta-catenin-sensitive transcription Cancer research 2001 61 1671 7 11245482
  45. [47]Wang K Ma Q Ren Y He J Zhang Y Zhang Y Geldanamycin destabilizes HER2 tyrosine kinase and suppresses Wnt/beta-catenin signaling in HER2 overexpressing human breast cancer cells Oncology reports 2007 17 89 96 17143483
  46. [48]Tan X Apte U Micsenyi A Kotsagrelos E Luo JH Ranganathan S Epidermal growth factor receptor: a novel target of the Wnt/beta-catenin pathway in liver Gastroenterology 2005 129 285 302 16012954 PMC1821080
  47. [49]Boon EM van der Neut R van de Wetering M Clevers H Pals ST Wnt signaling regulates expression of the receptor tyrosine kinase met in colorectal cancer Cancer research 2002 62 5126 8 12234972
  48. [50]Rodilla V Villanueva A Obrador-Hevia A Robert-Moreno A Fernandez-Majada V Grilli A Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer Proc Natl Acad Sci U S A 2009 106 6315 20 19325125 PMC2669348
  49. [51]Koh TJ Bulitta CJ Fleming JV Dockray GJ Varro A Wang TC Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis J Clin Invest 2000 106 533 9 10953028 PMC380254
  50. [52]Brabletz T Jung A Dag S Hlubek F Kirchner T beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer Am J Pathol 1999 155 1033 8 10514384 PMC1867011
  51. [53]Zhang T Otevrel T Gao Z Gao Z Ehrlich SM Fields JZ Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer Cancer research 2001 61 8664 7 11751382
  52. [54]Hendrix ND Wu R Kuick R Schwartz DR Fearon ER Cho KR Fibroblast growth factor 9 has oncogenic activity and is a downstream target of Wnt signaling in ovarian endometrioid adenocarcinomas Cancer research 2006 66 1354 62 16452189
  53. [55]Chamorro MN Schwartz DR Vonica A Brivanlou AH Cho KR Varmus HE FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development Embo J 2005 24 73 84 15592430 PMC544900
  54. [56]Shimokawa T Furukawa Y Sakai M Li M Miwa N Lin YM Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the beta-catenin/T-cell factor complex Cancer research 2003 63 6116 20 14559787
  55. [57]Shtutman M Zhurinsky J Simcha I Albanese C D’Amico M Pestell R The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway Proc Natl Acad Sci U S A 1999 96 5522 7 10318916 PMC21892
  56. [58]Tetsu O McCormick F Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells Nature 1999 398 422 6 10201372
  57. [59]He TC Sparks AB Rago C Hermeking H Zawel L da Costa LT Identification of c-MYC as a target of the APC pathway Science (New York, NY 1998 281 1509 12 9727977
  58. [60]Cadoret A Ovejero C Terris B Souil E Levy L Lamers WH New targets of beta-catenin signaling in the liver are involved in the glutamine metabolism Oncogene 2002 21 8293 301 12447692
  59. [61]Giera S Braeuning A Kohle C Bursch W Metzger U Buchmann A Wnt/beta-catenin signaling activates and determines hepatic zonal expression of glutathione S-transferases in mouse liver Toxicol Sci 2010 115 22 33 20118494
  60. [62]Loeppen S Koehle C Buchmann A Schwarz M A beta-catenin-dependent pathway regulates expression of cytochrome P450 isoforms in mouse liver tumors Carcinogenesis 2005 26 239 48 15471898
  61. [63]Nejak-Bowen K Monga SP Wnt/beta-catenin signaling in hepatic organogenesis Organogenesis 2008 4 92 9 19279720 PMC2634254
  62. [64]Ovejero C Cavard C Perianin A Hakvoort T Vermeulen J Godard C Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of beta-catenin in the liver Hepatology 2004 40 167 76 15239100
  63. [65]Sekine S Lan BY Bedolli M Feng S Hebrok M Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice Hepatology 2006 43 817 25 16557553
  64. [66]Tan X Behari J Cieply B Michalopoulos GK Monga SP Conditional deletion of beta-catenin reveals its role in liver growth and regeneration Gastroenterology 2006 131 1561 72 17101329
  65. [67]Leung JY Kolligs FT Wu R Zhai Y Kuick R Hanash S Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling J Biol Chem 2002 277 21657 65 11940574
  66. [68]Roose J Huls G van Beest M Moerer P van der Horn K Goldschmeding R Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1 Science (New York, NY) 1999 285 1923 6 10489374
  67. [69]Cadigan KM Fish MP Rulifson EJ Nusse R Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing Cell 1998 93 767 77 9630221
  68. [70]Khan Z Vijayakumar S de la Torre TV Rotolo S Bafico A Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor Mol Cell Biol 2007 27 7291 301 17698587 PMC2168903
  69. [71]Austinat M Dunsch R Wittekind C Tannapfel A Gebhardt R Gaunitz F Correlation between beta-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma Mol Cancer 2008 7 21 18282277 PMC2287186
  70. [72]Cieply B Zeng G Proverbs-Singh T Geller DA Monga SP Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin gene Hepatology 2009 49 821 31 19101982 PMC2657345
  71. [73]Hoshida Y Nijman SM Kobayashi M Chan JA Brunet JP Chiang DY Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma Cancer research 2009 69 7385 92 19723656 PMC3549578
  72. [74]Hsu HC Jeng YM Mao TL Chu JS Lai PL Peng SY Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis Am J Pathol 2000 157 763 70 10980116 PMC1885685
  73. [75]Zucman-Rossi J Benhamouche S Godard C Boyault S Grimber G Balabaud C Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas Oncogene 2007 26 774 80 16964294
  74. [76]Hovanes K Li TW Munguia JE Truong T Milovanovic T Lawrence Marsh J Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer Nat Genet 2001 28 53 7 11326276
  75. [77]MacDonald BT Tamai K He X Wnt/beta-catenin signaling: components, mechanisms, and diseases Dev Cell 2009 17 9 26 19619488 PMC2861485
  76. [78]Michalopoulos GK DeFrances MC Liver regeneration Science (New York, NY) 1997 276 60 6 9082986
  77. [81]Taub R Liver regeneration 4: transcriptional control of liver regeneration Faseb J 1996 10 413 27 8647340
  78. [82]Su AI Guidotti LG Pezacki JP Chisari FV Schultz PG Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice Proc Natl Acad Sci U S A 2002 99 11181 6 12177410 PMC123230
  79. [83]White P Brestelli JE Kaestner KH Greenbaum LE Identification of transcriptional networks during liver regeneration J Biol Chem 2005 280 3715 22 15546871
  80. [84]Walker PR Potter VR Isozyme studies on adult, regenerating, precancerous and developing liver in relation to findings in hepatomas Advances in enzyme regulation 1972 10 339 64 4347316
  81. [85]Rabes HM Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver Ciba Found Symp 1977 31 53 248005
  82. [86]Stocker E Heine WD Regeneration of liver parenchyma under normal and pathological conditions Beitr Pathol 1971 144 400 8 5158468
  83. [87]Stocker E Wullstein HK Brau G Capacity of regeneration in liver epithelia of juvenile, repeated partially hepatectomized rats. Autoradiographic studies after continous infusion of 3H-thymidine (author’s transl) Virchows Arch B Cell Pathol 1973 14 93 103 4203888
  84. [88]Grisham JW A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3 Cancer research 1962 22 842 9 13902009
  85. [89]Nelsen CJ Rickheim DG Timchenko NA Stanley MW Albrecht JH Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo Cancer research 2001 61 8564 8 11731443
  86. [91]Cadoret A Ovejero C Saadi-Kheddouci S Souil E Fabre M Romagnolo B Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin Cancer research 2001 61 3245 9 11309273
  87. [92]Harada N Miyoshi H Murai N Oshima H Tamai Y Oshima M Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin Cancer research 2002 62 1971 7 11929813
  88. [93]Monga SP Pediaditakis P Mule K Stolz DB Michalopoulos GK Changes in WNT/beta-catenin pathway during regulated growth in rat liver regeneration Hepatology 2001 33 1098 109 11343237 PMC1821078
  89. [94]Pediaditakis P Lopez-Talavera JC Petersen B Monga SP Michalopoulos GK The processing and utilization of hepatocyte growth factor/scatter factor following partial hepatectomy in the rat Hepatology 2001 34 688 93 11584364 PMC1821089
  90. [95]Haegel H Larue L Ohsugi M Fedorov L Herrenknecht K Kemler R Lack of beta-catenin affects mouse development at gastrulation Development (Cambridge, England) 1995 121 3529 37 8582267
  91. [96]Grigoryan T Wend P Klaus A Birchmeier W Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice Genes Dev 2008 22 2308 41 18765787 PMC2749675
  92. [97]Sodhi D Micsenyi A Bowen WC Monga DK Talavera JC Monga SP Morpholino oligonucleotide-triggered beta-catenin knockdown compromises normal liver regeneration Journal of hepatology 2005 43 132 41 15893845
  93. [98]Sekine S Gutierrez PJ Lan BY Feng S Hebrok M Liver-specific loss of beta-catenin results in delayed hepatocyte proliferation after partial hepatectomy Hepatology 2007 45 361 8 17256747
  94. [99]Apte U Singh S Zeng G Cieply B Virji MA Wu T Beta-catenin activation promotes liver regeneration after acetaminophen-induced injury Am J Pathol 2009 175 1056 65 19679878 PMC2731124
  95. [100]Colnot S Decaens T Niwa-Kawakita M Godard C Hamard G Kahn A Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas Proc Natl Acad Sci U S A 2004 101 17216 21 15563600 PMC535370
  96. [101]Goessling W North TE Lord AM Ceol C Lee S Weidinger G APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development Dev Biol 2008 320 161 74 18585699
  97. [102]Qian J Sarnaik AA Bonney TM Keirsey J Combs KA Steigerwald K The APC tumor suppressor inhibits DNA replication by directly binding to DNA via its carboxyl terminus Gastroenterology 2008 135 152 62 18474248 PMC2832605
  98. [103]Prosperi JR Becher KR Willson TA Collins MH Witte DP Goss KH The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland J Cell Physiol 2009 220 319 31 19326388
  99. [104]Nejak-Bowen KN Thompson MD Singh S Bowen WC Jr Dar MJ Khillan J Accelerated liver regeneration and hepatocarcinogenesis in mice overexpressing serine-45 mutant beta-catenin Hepatology 2010 51 1603 13 20432254 PMC2908905
  100. [105]Manisastry SM Han M Linask KK Early temporal-specific responses and differential sensitivity to lithium and Wnt-3A exposure during heart development Dev Dyn 2006 235 2160 74 16804895
  101. [106]Matthews VB Yeoh GC Liver stem cells IUBMB Life 2005 57 549 53 16118112
  102. [107]Oertel M Shafritz DA Stem cells, cell transplantation and liver repopulation Biochim Biophys Acta 2008 1782 61 74 18187050 PMC2857398
  103. [108]Oh SH Hatch HM Petersen BE Hepatic oval ‘stem’ cell in liver regeneration Semin Cell Dev Biol 2002 13 405 9 12468240
  104. [109]Farber E Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3′-methyl-4-dimethylaminoazobenzene Cancer research 1956 16 142 8 13293655
  105. [110]Kuwahara R Kofman AV Landis CS Swenson ES Barendswaard E Theise ND The hepatic stem cell niche: identification by label-retaining cell assay Hepatology 2008 47 1994 2002 18454509 PMC2847183
  106. [111]Sell S Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury Hepatology 1998 27 317 31 9462626
  107. [112]Yovchev MI Grozdanov PN Zhou H Racherla H Guha C Dabeva MD Identification of adult hepatic progenitor cells capable of repopulating injured rat liver Hepatology 2008 47 636 47 18023068
  108. [113]Sell S Leffert HL Liver cancer stem cells J Clin Oncol 2008 26 2800 5 18539957 PMC2515096
  109. [114]Roskams T Liver stem cells and their implication in hepatocellular and cholangiocarcinoma Oncogene 2006 25 3818 22 16799623
  110. [115]de Lima VM Oliveira CP Alves VA Chammas MC Oliveira EP Stefano JT A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma Journal of hepatology 2008 49 1055 61 18929425
  111. [116]Bennoun M Rissel M Engelhardt N Guillouzo A Briand P Weber-Benarous A Oval cell proliferation in early stages of hepatocarcinogenesis in simian virus 40 large T transgenic mice Am J Pathol 1993 143 1326 36 7694468 PMC1887169
  112. [117]Evarts RP Nagy P Marsden E Thorgeirsson SS A precursor-product relationship exists between oval cells and hepatocytes in rat liver Carcinogenesis 1987 8 1737 40 3664968
  113. [118]Paku S Schnur J Nagy P Thorgeirsson SS Origin and structural evolution of the early proliferating oval cells in rat liver Am J Pathol 2001 158 1313 23 11290549 PMC1891899
  114. [119]Petersen BE Zajac VF Michalopoulos GK Bile ductular damage induced by methylene dianiline inhibits oval cell activation Am J Pathol 1997 151 905 9 9327722 PMC1858051
  115. [120]Akhurst B Croager EJ Farley-Roche CA Ong JK Dumble ML Knight B A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver Hepatology 2001 34 519 22 11526537
  116. [121]Preisegger KH Factor VM Fuchsbichler A Stumptner C Denk H Thorgeirsson SS Atypical ductular proliferation and its inhibition by transforming growth factor beta1 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic alcoholic liver disease Lab Invest 1999 79 103 9 10068199
  117. [122]Jelnes P Santoni-Rugiu E Rasmussen M Friis SL Nielsen JH Tygstrup N Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration Hepatology 2007 45 1462 70 17538966
  118. [123]Fausto N Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells Hepatology 2004 39 1477 87 15185286
  119. [124]Lazaro CA Rhim JA Yamada Y Fausto N Generation of hepatocytes from oval cell precursors in culture Cancer research 1998 58 5514 22 9850088
  120. [125]Alison MR Islam S Lim S Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly J Pathol 2009 217 282 98 18991329
  121. [126]Sell S Cellular origin of hepatocellular carcinomas Semin Cell Dev Biol 2002 13 419 24 12468242
  122. [127]Ma S Chan KW Hu L Lee TK Wo JY Ng IO Identification and characterization of tumorigenic liver cancer stem/progenitor cells Gastroenterology 2007 132 2542 56 17570225
  123. [128]Suetsugu A Nagaki M Aoki H Motohashi T Kunisada T Moriwaki H Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells Biochem Biophys Res Commun 2006 351 820 4 17097610
  124. [129]Rountree CB Senadheera S Mato JM Crooks GM Lu SC Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice Hepatology 2008 47 1288 97 18167064 PMC2408692
  125. [130]Lee JS Heo J Libbrecht L Chu IS Kaposi-Novak P Calvisi DF A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells Nat Med 2006 12 410 6 16532004
  126. [131]Vander Borght S Komuta M Libbrecht L Katoonizadeh A Aerts R Dymarkowski S Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin Liver Int 2008 28 1370 80 19055643
  127. [132]Yamashita T Ji J Budhu A Forgues M Yang W Wang HY EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features Gastroenterology 2009 136 1012 24 19150350 PMC2828822
  128. [133]Yamashita T Budhu A Forgues M Wang XW Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma Cancer research 2007 67 10831 9 18006828
  129. [134]Fodde R Brabletz T Wnt/beta-catenin signaling in cancer stemness and malignant behavior Curr Opin Cell Biol 2007 19 150 8 17306971
  130. [135]Nusse R Fuerer C Ching W Harnish K Logan C Zeng A Wnt signaling and stem cell control Cold Spring Harb Symp Quant Biol 2008 73 59 66 19028988
  131. [136]Hu M Kurobe M Jeong YJ Fuerer C Ghole S Nusse R Wnt/beta-catenin signaling in murine hepatic transit amplifying progenitor cells Gastroenterology 2007 133 1579 91 17983805
  132. [137]Apte U Thompson MD Cui S Liu B Cieply B Monga SP Wnt/beta-catenin signaling mediates oval cell response in rodents Hepatology 2008 47 288 95 17929301
  133. [138]Zhang Y Li XM Zhang FK Wang BE Activation of canonical Wnt signaling pathway promotes proliferation and self-renewal of rat hepatic oval cell line WB-F344 in vitro World J Gastroenterol 2008 14 6673 80 19034970 PMC2773309
  134. [139]Itoh T Kamiya Y Okabe M Tanaka M Miyajima A Inducible expression of Wnt genes during adult hepatic stem/progenitor cell response FEBS Lett 2009 583 777 81 19174158
  135. [140]Williams JM Oh SH Jorgensen M Steiger N Darwiche H Shupe T The role of the Wnt family of secreted proteins in rat oval “stem” cell-based liver regeneration: Wnt1 drives differentiation Am J Pathol 2010 176 2732 42 20413689 PMC2877835
  136. [141]Spee B Carpino G Schotanus BA Katoonizadeh A Vander Borght S Gaudio E Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling Gut 2010 59 247 57 19880964
  137. [142]Chiba T Zheng YW Kita K Yokosuka O Saisho H Onodera M Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation Gastroenterology 2007 133 937 50 17673212
  138. [143]Yang W Yan HX Chen L Liu Q He YQ Yu LX Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells Cancer research 2008 68 4287 95 18519688
  139. [144]Kitisin K Pishvaian MJ Johnson LB Mishra L Liver stem cells and molecular signaling pathways in hepatocellular carcinoma Gastrointest Cancer Res 2007 1 S13 21 19360142 PMC2666844
  140. [145]Ferlay J Shin HR Bray F Forman D Mathers C Parkin DM Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 Int J Cancer 2010 21351269
  141. [146]Farazi PA DePinho RA Hepatocellular carcinoma pathogenesis: from genes to environment Nat Rev Cancer 2006 6 674 87 16929323
  142. [147]Villanueva A Newell P Chiang DY Friedman SL Llovet JM Genomics and signaling pathways in hepatocellular carcinoma Semin Liver Dis 2007 27 55 76 17295177
  143. [148]Wong CM Ng IO Molecular pathogenesis of hepatocellular carcinoma Liver Int 2008 28 160 74 18069974
  144. [149]Lok AS Seeff LB Morgan TR di Bisceglie AM Sterling RK Curto TM Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease Gastroenterology 2009 136 138 48 18848939 PMC3749922
  145. [150]Vogelstein B Kinzler KW Cancer genes and the pathways they control Nat Med 2004 10 789 99 15286780
  146. [151]Bressac B Kew M Wands J Ozturk M Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa Nature 1991 350 429 31 1672732
  147. [152]Hsu IC Metcalf RA Sun T Welsh JA Wang NJ Harris CC Mutational hotspot in the p53 gene in human hepatocellular carcinomas Nature 1991 350 427 8 1849234
  148. [153]de La Coste A Romagnolo B Billuart P Renard CA Buendia MA Soubrane O Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas Proc Natl Acad Sci U S A 1998 95 8847 51 9671767 PMC21165
  149. [154]Yao YJ Ping XL Zhang H Chen FF Lee PK Ahsan H PTEN/MMAC1 mutations in hepatocellular carcinomas Oncogene 1999 18 3181 5 10340391
  150. [155]Zender L Villanueva A Tovar V Sia D Chiang DY Llovet JM Cancer gene discovery in hepatocellular carcinoma Journal of hepatology 2010 52 921 9 20385424 PMC2905725
  151. [156]Finn RS Zhu AX Targeting angiogenesis in hepatocellular carcinoma: focus on VEGF and bevacizumab Expert Rev Anticancer Ther 2009 9 503 9 19374603
  152. [157]Harada N Oshima H Katoh M Tamai Y Oshima M Taketo MM Hepatocarcinogenesis in mice with beta-catenin and Ha-ras gene mutations Cancer research 2004 64 48 54 14729607
  153. [158]Miyoshi H Deguchi A Nakau M Kojima Y Mori A Oshima M Hepatocellular carcinoma development induced by conditional beta-catenin activation in Lkb1+/− mice Cancer Sci 2009 100 2046 53 19671058 PMC11159713
  154. [159]Bauer-Hofmann R Klimek F Buchmann A Muller O Bannasch P Schwarz M Role of mutations at codon 61 of the c-Ha-ras gene during diethylnitrosamine-induced hepatocarcinogenesis in C3H/He mice Mol Carcinog 1992 6 60 7 1323970
  155. [160]Haramis AP Hurlstone A van der Velden Y Begthel H van den Born M Offerhaus GJ Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia EMBO Rep 2006 7 444 9 16439994 PMC1456916
  156. [161]Aydinlik H Nguyen TD Moennikes O Buchmann A Schwarz M Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors Oncogene 2001 20 7812 6 11753661
  157. [162]Schwarz M Wanke I Wulbrand U Moennikes O Buchmann A Role of connexin32 and beta-catenin in tumor promotion in mouse liver Toxicol Pathol 2003 31 99 102 12597453
  158. [163]Ogawa K Yamada Y Kishibe K Ishizaki K Tokusashi Y Beta-catenin mutations are frequent in hepatocellular carcinomas but absent in adenomas induced by diethylnitrosamine in B6C3F1 mice Cancer research 1999 59 1830 3 10213486
  159. [164]Devereux TR Anna CH Foley JF White CM Sills RC Barrett JC Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis Oncogene 1999 18 4726 33 10467420
  160. [165]Calvisi DF Ladu S Factor VM Thorgeirsson SS Activation of beta-catenin provides proliferative and invasive advantages in c-myc/TGF-alpha hepatocarcinogenesis promoted by phenobarbital Carcinogenesis 2004 25 901 8 14742323
  161. [166]Calvisi DF Conner EA Ladu S Lemmer ER Factor VM Thorgeirsson SS Activation of the canonical Wnt/beta-catenin pathway confers growth advantages in c-Myc/E2F1 transgenic mouse model of liver cancer Journal of hepatology 2005 42 842 9 15885355
  162. [167]Calvisi DF Factor VM Loi R Thorgeirsson SS Activation of beta-catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade Cancer research 2001 61 2085 91 11280770
  163. [168]Zulehner G Mikula M Schneller D van Zijl F Huber H Sieghart W Nuclear beta-catenin induces an early liver progenitor phenotype in hepatocellular carcinoma and promotes tumor recurrence Am J Pathol 2010 176 472 81 20008139 PMC2797905
  164. [169]Zhang XF Tan X Zeng G Misse A Singh S Kim Y Conditional beta-catenin loss in mice promotes chemical hepatocarcinogenesis: role of oxidative stress and platelet-derived growth factor receptor alpha/phosphoinositide 3-kinase signaling Hepatology 2010 52 954 65 20583210 PMC3100799
  165. [170]Rignall B Braeuning A Buchmann A Schwarz M Tumor Formation in Liver of Conditional {beta}-Catenin-Deficient Mice Exposed to a Diethylnitrosamine/Phenobarbital Tumor Promotion Regimen Carcinogenesis 2010 21047994
  166. [171]Fujie H Moriya K Shintani Y Tsutsumi T Takayama T Makuuchi M Frequent beta-catenin aberration in human hepatocellular carcinoma Hepatol Res 2001 20 39 51 11282485
  167. [172]Huang H Fujii H Sankila A Mahler-Araujo BM Matsuda M Cathomas G Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection Am J Pathol 1999 155 1795 801 10595907 PMC1866943
  168. [173]Kim YD Park CH Kim HS Choi SK Rew JS Kim DY Genetic alterations of Wnt signaling pathway-associated genes in hepatocellular carcinoma J Gastroenterol Hepatol 2008 23 110 8 18171349
  169. [174]Kondo Y Kanai Y Sakamoto M Genda T Mizokami M Ueda R Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma Jpn J Cancer Res 1999 90 1301 9 10665646 PMC5926034
  170. [175]Satoh S Daigo Y Furukawa Y Kato T Miwa N Nishiwaki T AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1 Nat Genet 2000 24 245 50 10700176
  171. [176]Taniguchi K Roberts LR Aderca IN Dong X Qian C Murphy LM Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas Oncogene 2002 21 4863 71 12101426
  172. [177]Merle P de la Monte S Kim M Herrmann M Tanaka S Von Dem Bussche A Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma Gastroenterology 2004 127 1110 22 15480989
  173. [178]Nambotin SB Lefrancois L Sainsily X Berthillon P Kim M Wands JR Pharmacological inhibition of Frizzled-7 displays anti-tumor properties in hepatocellular carcinoma Journal of hepatology 2010 21055837
  174. [179]Ban KC Singh H Krishnan R Seow HF GSK-3beta phosphorylation and alteration of beta-catenin in hepatocellular carcinoma Cancer Lett 2003 199 201 8 12969793
  175. [180]Shih YL Shyu RY Hsieh CB Lai HC Liu KY Chu TY Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma Cancer 2006 107 579 90 16795071
  176. [181]Wong CM Fan ST Ng IO beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance Cancer 2001 92 136 45 11443619
  177. [182]Fukutomi T Zhou Y Kawai S Eguchi H Wands JR Li J Hepatitis C virus core protein stimulates hepatocyte growth: correlation with upregulation of wnt-1 expression Hepatology 2005 41 1096 105 15841445
  178. [183]Cha MY Kim CM Park YM Ryu WS Hepatitis B virus X protein is essential for the activation of Wnt/beta-catenin signaling in hepatoma cells Hepatology 2004 39 1683 93 15185310
  179. [184]Lian Z Liu J Li L Li X Clayton M Wu MC Enhanced cell survival of Hep3B cells by the hepatitis B x antigen effector, URG11, is associated with upregulation of beta-catenin Hepatology 2006 43 415 24 16496348
  180. [186]Paul S Dey A Wnt signaling and cancer development: therapeutic implication Neoplasma 2008 55 165 76 18348648
  181. [187]Monga SP Role of Wnt/beta-catenin signaling in liver metabolism and cancer Int J Biochem Cell Biol 2009 PMC2891959 19747566
  182. [188]Boyault S Rickman DS de Reynies A Balabaud C Rebouissou S Jeannot E Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets Hepatology 2007 45 42 52 17187432
  183. [189]Audard V Grimber G Elie C Radenen B Audebourg A Letourneur F Cholestasis is a marker for hepatocellular carcinomas displaying beta-catenin mutations J Pathol 2007 212 345 52 17487939
  184. [190]Nhieu JT Renard CA Wei Y Cherqui D Zafrani ES Buendia MA Nuclear accumulation of mutated beta-catenin in hepatocellular carcinoma is associated with increased cell proliferation Am J Pathol 1999 155 703 10 10487827 PMC1866892
  185. [191]Park JY Park WS Nam SW Kim SY Lee SH Yoo NJ Mutations of beta-catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis Liver Int 2005 25 70 6 15698401
  186. [192]Suzuki T Yano H Nakashima Y Nakashima O Kojiro M Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process J Gastroenterol Hepatol 2002 17 994 1000 12167121
  187. [193]Mao TL Chu JS Jeng YM Lai PL Hsu HC Expression of mutant nuclear beta-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis J Pathol 2001 193 95 101 11169521
  188. [194]Yuan RH Jeng YM Chen HL Hsieh FJ Yang CY Lee PH Opposite roles of human pancreatitis-associated protein and REG1A expression in hepatocellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, beta-catenin mutation, and favorable prognosis Clin Cancer Res 2005 11 2568 75 15814635
  189. [195]Yuan RH Jeng YM Hu RH Lai PL Lee PH Cheng CC Role of p53 and beta-catenin Mutations in Conjunction with CK19 Expression on Early Tumor Recurrence and Prognosis of Hepatocellular Carcinoma J Gastrointest Surg 2010 21061181
  190. [196]Dal Bello B Rosa L Campanini N Tinelli C Torello Viera F D’Ambrosio G Glutamine synthetase immunostaining correlates with pathologic features of hepatocellular carcinoma and better survival after radiofrequency thermal ablation Clin Cancer Res 2010 16 2157 66 20233882
  191. [197]Zucman-Rossi J Jeannot E Nhieu JT Scoazec JY Guettier C Rebouissou S Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC Hepatology 2006 43 515 24 16496320
  192. [198]Llovet JM Bruix J Molecular targeted therapies in hepatocellular carcinoma Hepatology 2008 48 1312 27 18821591 PMC2597642
  193. [199]Yang JD Nakamura I Roberts LR The tumor microenvironment in hepatocellular carcinoma: Current status and therapeutic targets Semin Cancer Biol 2010 PMC3050428 20946957

Cited by

Sorted by citations

Authors
Nejak-Bowen, K. N., & Monga, S. P. S.
Affiliations
University of Pittsburgh (US)
Corresponding author
Monga, Satdarshan P.S.
ORCID
Monga, Satdarshan P.S.
Venue
Seminars in Cancer Biology
Publisher
Elsevier BV
Published
2011-02
Volume
21
Issue
1
Pages
44-58
ISSN
1044-579X (ISSN-L)
DOI
10.1016/j.semcancer.2010.12.010
PMC
PMC3050081
OpenAlex
W2054368385
Cited by
260
References
5
Citations by year
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FWCI
1.63
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Seminars in Cancer Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA124414)
  • National Institute of Diabetes and Digestive and Kidney Diseases (1 R01 DK62277, R01DK062277)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
β-catenin signaling, Wnt/β-catenin signaling, liver regeneration, hepatocellular carcinoma, hepatic oval cells, liver progenitor cells, chemical carcinogenesis, dysplasia, post-translational modification
MeSH terms
Animals, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Liver Regeneration, Stem Cells, Signal Transduction, Wnt Proteins, beta Catenin

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