Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review)

Katoh,Masaru

doi:10.3892/ijmm.2018.3689

August-2018 Volume 42 Issue 2

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August-2018 Volume 42 Issue 2

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Review Open Access

Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review)

Authors:
- Masaru Katoh
View Affiliations / Copyright

Affiliations: Department of Omics Network, National Cancer Center, Chuo Ward, Tokyo 104‑0045, Japan

Copyright: © Katoh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 713-725
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Published online on: May 17, 2018

https://doi.org/10.3892/ijmm.2018.3689
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Abstract

β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer. ABCB1, ALDH1A1, ASCL2, ATF3, AXIN2, BAMBI, CCND1, CD44, CLDN1, CTLA4, DKK1, EDN1, EOMES, FGF18, FGF20, FZD7, IL10, JAG1, LEF1, LGR5, MITF, MSX1, MYC, NEUROD1, NKD1, NODAL, NOTCH2, NOTUM, NRCAM, OPN, PAX3, PPARD, PTGS2, RNF43, SNAI1, SP5, TCF7, TERT, TNFRSF19, VEGFA and ZNRF3 are representative β‑catenin target genes. β‑catenin signaling is involved in myofibroblast activation and subsequent pulmonary fibrosis, in addition to other types of fibrosis. β‑catenin and NF‑κB signaling activation are involved in field cancerization in the stomach associated with Helicobacter pylori (H. pylori) infection and in the liver associated with hepatitis C virus (HCV) infection and other etiologies. β‑catenin‑targeted therapeutics are functionally classified into β‑catenin inhibitors targeting upstream regulators (AZ1366, ETC‑159, G007‑LK, GNF6231, ipafricept, NVP‑TNKS656, rosmantuzumab, vantictumab, WNT‑C59, WNT974 and XAV939), β‑catenin inhibitors targeting protein‑protein interactions (CGP049090, CWP232228, E7386, ICG‑001, LF3 and PRI‑724), β‑catenin inhibitors targeting epigenetic regulators (PKF118‑310), β‑catenin inhibitors targeting mediator complexes (CCT251545 and cortistatin A) and β‑catenin inhibitors targeting transmembrane‑type transcriptional outputs, including CD44v6, FZD7 and LGR5. Eradicating H. pylori and HCV is the optimal approach for the first‑line prevention of gastric cancer and hepatocellular carcinoma (HCC), respectively. However, β‑catenin inhibitors may be applicable for the prevention of organ fibrosis, second‑line HCC prevention and treating β‑catenin‑driven cancer. The multi‑layered prevention and treatment strategy of β‑catenin‑related human diseases is necessary for the practice of personalized medicine and implementation of precision medicine.

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1	Katoh M and Katoh M: Molecular genetics and targeted therapy of WNT-related human diseases (Review). Int J Mol Med. 40:587–606. 2017.PubMed/NCBI
2	Takeichi M: Dynamic contacts: Rearranging adherens junctions to drive epithelial remodelling. Nat Rev Mol Cell Biol. 15:397–410. 2014. View Article : Google Scholar : PubMed/NCBI
3	McCrea PD and Gottardi CJ: Beyond β-catenin: Prospects for a larger catenin network in the nucleus. Nat Rev Mol Cell Biol. 17:55–64. 2016. View Article : Google Scholar
4	Kufe DW: MUC1-C oncoprotein as a target in breast cancer: Activation of signaling pathways and therapeutic approaches. Oncogene. 32:1073–1081. 2013. View Article : Google Scholar
5	Liu Q, Cheng Z, Luo L, Yang Y, Zhang Z, Ma H, Chen T, Huang X, Lin SY, Jin M, et al: C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis. Oncotarget. 7:36800–36813. 2016.PubMed/NCBI
6	Klaus A and Birchmeier W: Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 8:387–398. 2008. View Article : Google Scholar : PubMed/NCBI
7	Vaquero J, Nguyen Ho-Bouldoires TH, Clapéron A and Fouassier L: Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: From signaling regulation to clinical relevance. Oncogene. 36:3067–3079. 2017. View Article : Google Scholar : PubMed/NCBI
8	Katoh M and Katoh M: WNT signaling pathway and stem cell signaling network. Clin Cancer Res. 13:4042–4045. 2007. View Article : Google Scholar : PubMed/NCBI
9	Valenta T, Hausmann G and Basler K: The many faces and functions of β-catenin. EMBO J. 31:2714–2736. 2012. View Article : Google Scholar : PubMed/NCBI
10	Lo YH, Noah TK, Chen MS, Zou W, Borras E, Vilar E and Shroyer NF: SPDEF induces quiescence of colorectal cancer cells by changing the transcriptional targets of β-catenin. Gastroenterology. 153:205–218.e8. 2017. View Article : Google Scholar
11	Frescas D and Pagano M: Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: Tipping the scales of cancer. Nat Rev Cancer. 8:438–449. 2008. View Article : Google Scholar : PubMed/NCBI
12	Novellasdemunt L, Foglizzo V, Cuadrado L, Antas P, Kucharska A, Encheva V, Snijders AP and Li VSW: USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating β-catenin deubiquitination. Cell Rep. 21:612–627. 2017. View Article : Google Scholar : PubMed/NCBI
13	Hoffmeyer K, Junghans D, Kanzler B and Kemler R: Trimethylation and acetylation of β-catenin at Lysine 49 represent key elements in ESC pluripotency. Cell Rep. 18:2815–2824. 2017. View Article : Google Scholar : PubMed/NCBI
14	Alok A, Lei Z, Jagannathan NS, Kaur S, Harmston N, Rozen SG, Tucker-Kellogg L and Virshup DM: Wnt proteins synergize to activate β-catenin signaling. J Cell Sci. 130:1532–1544. 2017. View Article : Google Scholar : PubMed/NCBI
15	Herbst A, Jurinovic V, Krebs S, Thieme SE, Blum H, Göke B and Kolligs FT: Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling. BMC Genomics. 15:742014. View Article : Google Scholar
16	Watanabe K, Biesinger J, Salmans ML, Roberts BS, Arthur WT, Cleary M, Andersen B, Xie X and Dai X: Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer. PLoS One. 9:e923172014. View Article : Google Scholar : PubMed/NCBI
17	Funa NS, Schachter KA, Lerdrup M, Ekberg J, Hess K, Dietrich N, Honoré C, Hansen K and Semb H: β-Catenin regulates primitive streak induction through collaborative interactions with SMAD2/SMAD3 and OCT4. Cell Stem Cell. 16:639–652. 2015. View Article : Google Scholar : PubMed/NCBI
18	Condello S, Morgan CA, Nagdas S, Cao L, Turek J, Hurley TD and Matei D: β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene. 34:2297–2308. 2015. View Article : Google Scholar
19	Spranger S, Bao R and Gajewski TF: Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 523:231–235. 2015. View Article : Google Scholar : PubMed/NCBI
20	Yun EJ, Zhou J, Lin CJ, Hernandez E, Fazli L, Gleave M and Hsieh JT: Targeting cancer stem cells in castration-resistant prostate cancer. Clin Cancer Res. 22:670–679. 2016. View Article : Google Scholar
21	Miwa N, Furuse M, Tsukita S, Niikawa N, Nakamura Y and Furukawa Y: Involvement of Claudin-1 in the β-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers. Oncol Res. 12:469–476. 2001. View Article : Google Scholar
22	Shah KV, Chien AJ, Yee C and Moon RT: CTLA-4 is a direct target of Wnt/β-catenin signaling and is expressed in human melanoma tumors. J Invest Dermatol. 128:2870–2879. 2008. View Article : Google Scholar : PubMed/NCBI
23	Yan KS, Janda CY, Chang J, Zheng GXY, Larkin KA, Luca VC, Chia LA, Mah AT, Han A, Terry JM, et al: Non-equivalence of Wnt and R-spondin ligands during Lgr5⁺ intestinal stem-cell self-renewal. Nature. 545:238–242. 2017. View Article : Google Scholar : PubMed/NCBI
24	Kaur A, Webster MR and Weeraratna AT: In the Wnt-er of life: Wnt signalling in melanoma and ageing. Br J Cancer. 115:1273–1279. 2016. View Article : Google Scholar : PubMed/NCBI
25	Ravindranath A, Yuen HF, Chan KK, Grills C, Fennell DA, Lappin TR and El-Tanani M: Wnt-β-catenin-Tcf-4 signalling-modulated invasiveness is dependent on osteopontin expression in breast cancer. Br J Cancer. 105:542–551. 2011. View Article : Google Scholar : PubMed/NCBI
26	Gnemmi V, Bouillez A, Gaudelot K, Hémon B, Ringot B, Pottier N, Glowacki F, Villers A, Vindrieux D, Cauffiez C, et al: MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter. Cancer Lett. 346:225–236. 2014. View Article : Google Scholar : PubMed/NCBI
27	Low KC and Tergaonkar V: Telomerase: Central regulator of all of the hallmarks of cancer. Trends Biochem Sci. 38:426–434. 2013. View Article : Google Scholar : PubMed/NCBI
28	Schön S, Flierman I, Ofner A, Stahringer A, Holdt LM, Kolligs FT and Herbst A: β-catenin regulates NF-κB activity via TNFRSF19 in colorectal cancer cells. Int J Cancer. 135:1800–1811. 2014. View Article : Google Scholar
29	De Jaime-Soguero A, Aulicino F, Ertaylan G, Griego A, Cerrato A, Tallam A, Del Sol A, Cosma MP and Lluis F: Wnt/Tcf1 pathway restricts embryonic stem cell cycle through activation of the Ink4/Arf locus. PLoS Genet. 13:e10066822017. View Article : Google Scholar : PubMed/NCBI
30	Ring A, Kim YM and Kahn M: Wnt/catenin signaling in adult stem cell physiology and disease. Stem Cell Rev Rep. 10:512–525. 2014. View Article : Google Scholar
31	Bataller R and Brenner DA: Liver fibrosis. J Clin Invest. 115:209–218. 2005. View Article : Google Scholar : PubMed/NCBI
32	Wynn TA and Ramalingam TR: Mechanisms of fibrosis: Therapeutic translation for fibrotic disease. Nat Med. 18:1028–1040. 2012. View Article : Google Scholar : PubMed/NCBI
33	Monga SP: β-catenin signaling and roles in liver homeostasis, injury, and tumorigenesis. Gastroenterology. 148:1294–1310. 2015. View Article : Google Scholar : PubMed/NCBI
34	Katoh M: Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity. Int J Oncol. 51:1357–1369. 2017. View Article : Google Scholar : PubMed/NCBI
35	Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, et al: Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 44:694–698. 2012. View Article : Google Scholar : PubMed/NCBI
36	Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al: Mutational landscape and significance across 12 major cancer types. Nature. 502:333–339. 2013. View Article : Google Scholar : PubMed/NCBI
37	Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI
38	Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, et al: Integrative clinical genomics of advanced prostate cancer. Cell. 161:1215–1228. 2015. View Article : Google Scholar : PubMed/NCBI
39	Teo AE, Garg S, Shaikh LH, Zhou J, Karet Frankl FE, Gurnell M, Happerfield L, Marker A, Bienz M, Azizan EA and Brown MJ: Pregnancy, primary aldosteronism, and adrenal CTNNB1 mutations. N Engl J Med. 373:1429–1436. 2015. View Article : Google Scholar : PubMed/NCBI
40	Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, et al: Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 531:47–52. 2016. View Article : Google Scholar : PubMed/NCBI
41	Cancer Genome Atlas Network: Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 517:576–582. 2015. View Article : Google Scholar : PubMed/NCBI
42	Cancer Genome Atlas Research Network; Asan University; BC Cancer Agency; Brigham and Women's Hospital; Broad Institute; Brown University; Case Western Reserve University; Dana-Farber Cancer Institute; Duke University; et al: Integrated genomic characterization of oesophageal carcinoma. Nature. 541:169–175. 2017. View Article : Google Scholar : PubMed/NCBI
43	Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, Srinivasan P, Gao J, Chakravarty D, Devlin SM, et al: Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 23:703–713. 2017. View Article : Google Scholar : PubMed/NCBI
44	Kaur A, Webster MR, Marchbank K, Behera R, Ndoye A, Kugel CH III, Dang VM, Appleton J, O'Connell MP, Cheng P, et al: sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. Nature. 532:250–254. 2016. View Article : Google Scholar : PubMed/NCBI
45	Webster MR, Kugel CH III and Weeraratna AT: The Wnts of change: How Wnts regulate phenotype switching in melanoma. Biochim Biophys Acta. 1856:244–251. 2015.PubMed/NCBI
46	Bui T, Schade B, Cardiff RD, Aina OH, Sanguin-Gendreau V and Muller WJ: β-Catenin haploinsufficiency promotes mammary tumorigenesis in an ErbB2-positive basal breast cancer model. Proc Natl Acad Sci USA. 114:E707–E716. 2017. View Article : Google Scholar
47	Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, Marotz C, Giannopoulou E, Chakravarthi BV, Varambally S, et al: Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 22:298–305. 2016. View Article : Google Scholar : PubMed/NCBI
48	Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, et al: Recurrent and functional regulatory mutations in breast cancer. Nature. 547:55–60. 2017. View Article : Google Scholar : PubMed/NCBI
49	Bugaytsova JA, Björnham O, Chernov YA, Gideonsson P, Henriksson S, Mendez M, Sjöström R, Mahdavi J, Shevtsova A, Ilver D, et al: Helicobacter pylori adapts to chronic infection and gastric disease via pH-responsive BabA-mediated adherence. Cell Host Microbe. 21:376–389. 2017. View Article : Google Scholar : PubMed/NCBI
50	Javaheri A, Kruse T, Moonens K, Mejías-Luque R, Debraekeleer A, Asche CI, Tegtmeyer N, Kalali B, Bach NC, Sieber SA, et al: Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nat Microbiol. 2:161892016. View Article : Google Scholar : PubMed/NCBI
51	Salama NR, Hartung ML and Müller A: Life in the human stomach: Persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol. 11:385–399. 2013. View Article : Google Scholar : PubMed/NCBI
52	Yamaoka Y and Graham DY: Helicobacter pylori virulence and cancer pathogenesis. Future Oncol. 10:1487–1500. 2014. View Article : Google Scholar : PubMed/NCBI
53	Käbisch R, Mejías-Luque R, Gerhard M and Prinz C: Involvement of Toll-like receptors on Helicobacter pylori-induced immunity. PLoS One. 9:e1048042014. View Article : Google Scholar : PubMed/NCBI
54	McCracken KW, Catá EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, Tsai YH, Mayhew CN, Spence JR, Zavros Y and Wells JM: Modelling human development and disease in pluripotent stem cell-derived gastric organoids. Nature. 516:400–404. 2014. View Article : Google Scholar : PubMed/NCBI
55	Bertaux-Skeirik N, Feng R, Schumacher MA, Li J, Mahe MM, Engevik AC, Javier JE, Peek RM Jr, Ottemann K, Orian-Rousseau V, et al: CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation. PLoS Pathog. 112:e10046632015. View Article : Google Scholar
56	Song X, Xin N, Wang W and Zhao C: Wnt/β-catenin, an oncogenic pathway targeted by H. pylori in gastric carcinogenesis. Oncotarget. 6:35579–35588. 2015. View Article : Google Scholar : PubMed/NCBI
57	Sigal M, Logan CY, Kapalczynska M, Mollenkopf HJ, Berger H, Wiedenmann B, Nusse R, Amieva MR and Meyer TF: Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis. Nature. 548:451–455. 2017. View Article : Google Scholar : PubMed/NCBI
58	Katoh M, Hirai M, Sugimura T and Terada M: Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family. Oncogene. 13:873–876. 1996.PubMed/NCBI
59	Katoh M, Kirikoshi H, Terasaki H and Shiokawa K: WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT-β-catenin-TCF signaling pathway. Biochem Biophys Res Commun. 289:1093–1098. 2001. View Article : Google Scholar : PubMed/NCBI
60	Jiang X and Cong F: Novel regulation of Wnt signaling at the proximal membrane level. Trends Biochem Sci. 41:773–783. 2016. View Article : Google Scholar : PubMed/NCBI
61	Milne AN, Carneiro F, O'Morain C and Offerhaus GJ: Nature meets nurture: Molecular genetics of gastric cancer. Hum Genet. 126:615–628. 2009. View Article : Google Scholar : PubMed/NCBI
62	Leodolter A, Alonso S, González B, Ebert MP, Vieth M, Röcken C, Wex T, Peitz U, Malfertheiner P and Perucho M: Somatic DNA hypomethylation in H. pylori-associated high-risk gastritis and gastric cancer: Enhanced somatic hypomethylation associates with advanced stage cancer. Clin Transl Gastroenterol. 6:e852015. View Article : Google Scholar : PubMed/NCBI
63	Ajani JA, Lee J, Sano T, Janjigian YY, Fan D and Song S: Gastric adenocarcinoma. Nat Rev Dis Primers. 3:170362017. View Article : Google Scholar : PubMed/NCBI
64	Huh CW, Youn YH, Jung da H, Park JJ, Kim JH and Park H: Early attempts to eradicate Helicobacter pylori after endoscopic resection of gastric neoplasm significantly improve eradication success rates. PLoS One. 11:e01622582016. View Article : Google Scholar : PubMed/NCBI
65	Dang BN and Graham DY: Helicobacter pylori infection and antibiotic resistance: A WHO high priority? Nat Rev Gastroenterol Hepatol. 14:383–384. 2017. View Article : Google Scholar : PubMed/NCBI
66	Osumi H, Fujisaki J, Suganuma T, Horiuchi Y, Omae M, Yoshio T, Ishiyama A, Tsuchida T and Miki K: A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successfulHelicobacter pylori eradication. PLoS One. 12:e01839802017. View Article : Google Scholar
67	Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y and Nakayama T: Effectiveness of Helicobacter pylori eradication in the prevention of primary gastric cancer in healthy asymptomatic people: A systematic review and meta-analysis comparing risk ratio with risk difference. PLoS One. 12:e01833212017. View Article : Google Scholar : PubMed/NCBI
68	Smyth MJ, Ngiow SF, Ribas A and Teng MW: Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol. 13:143–158. 2016. View Article : Google Scholar
69	Arzumanyan A, Reis HM and Feitelson MA: Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 13:123–135. 2013. View Article : Google Scholar : PubMed/NCBI
70	Touboul T, Chen S, To CC, Mora-Castilla S, Sabatini K, Tukey RH and Laurent LC: Stage-specific regulation of the WNT/β-catenin pathway enhances differentiation of hESCs into hepatocytes. J Hepatol. 64:1315–1326. 2016. View Article : Google Scholar : PubMed/NCBI
71	Planas-Paz L, Orsini V, Boulter L, Calabrese D, Pikiolek M, Nigsch F, Xie Y, Roma G, Donovan A, Marti P, et al: The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size. Nat Cell Biol. 18:467–479. 2016. View Article : Google Scholar : PubMed/NCBI
72	Okabe H, Yang J, Sylakowski K, Yovchev M, Miyagawa Y, Nagarajan S, Chikina M, Thompson M, Oertel M, Baba H, et al: Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice. Hepatology. 64:1652–1666. 2016. View Article : Google Scholar : PubMed/NCBI
73	Li J, Hu SB, Wang LY, Zhang X, Zhou X, Yang B, Li JH, Xiong J, Liu N, Li Y, et al: Autophagy-dependent generation of Axin2⁺ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis. Oncogene. 36:6725–6737. 2017. View Article : Google Scholar : PubMed/NCBI
74	Kuijk EW, Rasmussen S, Blokzijl F, Huch M, Gehart H, Toonen P, Begthel H, Clevers H, Geurts AM and Cuppen E: Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure. Sci Rep. 6:221542016. View Article : Google Scholar : PubMed/NCBI
75	Yin X, Yi H, Wang L, Wu W, Wu X and Yu L: RSPOs facilitated HSC activation and promoted hepatic fibrogenesis. Oncotarget. 7:63767–63778. 2016. View Article : Google Scholar : PubMed/NCBI
76	Tokunaga Y, Osawa Y, Ohtsuki T, Hayashi Y, Yamaji K, Yamane D, Hara M, Munekata K, Tsukiyama-Kohara K, Hishima T, et al: Selective inhibitor of Wnt/β-catenin/CBP signaling ameliorates hepatitis C virus-induced liver fibrosis in mouse model. Sci Rep. 7:3252017. View Article : Google Scholar
77	Tao J, Xu E, Zhao Y, Singh S, Li X, Couchy G, Chen X, Zucman-Rossi J, Chikina M and Monga SP: Modeling a human hepatocellular carcinoma subset in mice through coexpression of Met and point-mutant β-catenin. Hepatology. 64:1587–1605. 2016. View Article : Google Scholar : PubMed/NCBI
78	Zhang J, Lai W, Li Q, Yu Y, Jin J, Guo W, Zhou X, Liu X and Wang Y: A novel oncolytic adenovirus targeting Wnt signaling effectively inhibits cancer-stem like cell growth via metastasis, apoptosis and autophagy in HCC models. Biochem Biophys Res Commun. 491:469–477. 2017. View Article : Google Scholar : PubMed/NCBI
79	Lamb YN: Glecaprevir/pibrentasvir: First global approval. Drugs. 77:1797–1804. 2017. View Article : Google Scholar : PubMed/NCBI
80	Nehra V, Rizza SA and Temesgen Z: Sofosbuvir/velpatasvir fixed-dose combination for the treatment of chronic hepatitis C virus infection. Drugs Today (Barc). 53:177–189. 2017. View Article : Google Scholar
81	Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, Foschi FG, Lenzi M, Mazzella G, Verucchi G, et al: Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 65:727–733. 2016. View Article : Google Scholar : PubMed/NCBI
82	Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, Díaz A, Vilana R, Darnell A, Varela M, et al: Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 65:719–726. 2016. View Article : Google Scholar : PubMed/NCBI
83	Kobayashi M, Suzuki F, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Suzuki Y, Saitoh S, Arase Y, et al: Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection. J Med Virol. 89:476–483. 2017. View Article : Google Scholar
84	Selman M, López-Otín C and Pardo A: Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir J. 48:538–552. 2016. View Article : Google Scholar : PubMed/NCBI
85	Knudsen L, Ruppert C and Ochs M: Tissue remodelling in pulmonary fibrosis. Cell Tissue Res. 367:607–626. 2017. View Article : Google Scholar
86	Cao Z, Lis R, Ginsberg M, Chavez D, Shido K, Rabbany SY, Fong GH, Sakmar TP, Rafii S and Ding BS: Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. Nat Med. 22:154–162. 2016. View Article : Google Scholar : PubMed/NCBI
87	Andersson-Sjöland A, Karlsson JC and Rydell-Törmänen K: ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling. Lab Invest. 96:206–217. 2016. View Article : Google Scholar
88	Misharin AV, Morales-Nebreda L, Reyfman PA, Cuda CM, Walter JM, McQuattie-Pimentel AC, Chen CI, Anekalla KR, Joshi N, Williams KJN, et al: Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J Exp Med. 214:2387–2404. 2017. View Article : Google Scholar : PubMed/NCBI
89	Henderson WR Jr, Chi EY, Ye X, Nguyen C, Tien YT, Zhou B, Borok Z, Knight DA and Kahn M: Inhibition of Wnt/β-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci USA. 107:14309–14314. 2010. View Article : Google Scholar
90	Chen X, Shi C, Meng X, Zhang K, Li X, Wang C, Xiang Z, Hu K and Han X: Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2. Exp Mol Pathol. 101:22–30. 2016. View Article : Google Scholar : PubMed/NCBI
91	Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, Shukla SA, Guo G, Brooks AN, Murray BA, et al: Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 48:607–616. 2016. View Article : Google Scholar : PubMed/NCBI
92	Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, et al: A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 545:355–359. 2017. View Article : Google Scholar : PubMed/NCBI
93	Chartier C, Raval J, Axelrod F, Bond C, Cain J, Dee-Hoskins C, Ma S, Fischer MM, Shah J, Wei J, et al: Therapeutic targeting of tumor-derived R-Spondin attenuates β-catenin signaling and tumorigenesis in multiple cancer types. Cancer Res. 76:713–723. 2016. View Article : Google Scholar : PubMed/NCBI
94	Yang Y, Shen J, He J, He J and Jiang G: A meta-analysis of abnormal β-catenin immunohistochemical expression as a prognostic factor in lung cancer: Location is more important. Clin Transl Oncol. 18:685–692. 2016. View Article : Google Scholar
95	Jin J, Zhan P, Katoh M, Kobayashi SS, Phan K, Qian H, Li H and Wang X and Wang X: Prognostic significance of β-catenin expression in patients with non-small cell lung cancer: A meta-analysis. Transl Lung Cancer Res. 6:97–108. 2017. View Article : Google Scholar : PubMed/NCBI
96	Mano H: ALKoma: A cancer subtype with a shared target. Cancer Discov. 2:495–502. 2012. View Article : Google Scholar : PubMed/NCBI
97	Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, Lee J, Jung YJ, Kim JO, Shin JY, et al: The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 22:2109–2119. 2012. View Article : Google Scholar : PubMed/NCBI
98	Hirsch FR, Suda K, Wiens J and Bunn PA Jr: New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 388:1012–1024. 2016. View Article : Google Scholar : PubMed/NCBI
99	Katoh M: Therapeutics targeting FGF signaling network in human diseases. Trends Pharmacol Sci. 37:1081–1096. 2016. View Article : Google Scholar : PubMed/NCBI
100	Gurney A, Axelrod F, Bond CJ, Cain J, Chartier C, Donigan L, Fischer M, Chaudhari A, Ji M, Kapoun AM, et al: Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors. Proc Natl Acad Sci USA. 109:11717–11722. 2012. View Article : Google Scholar : PubMed/NCBI
101	Steinhart Z, Pavlovic Z, Chandrashekhar M, Hart T, Wang X, Zhang X, Robitaille M, Brown KR, Jaksani S, Overmeer R, et al: Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nat Med. 23:60–68. 2017. View Article : Google Scholar
102	Bendell J, Eckhardt GS, Hochster HS, Morris VK, Strickler J, Kapoun AM, Wang M, Xu L, McGuire K, Dupont J, et al: Initial results from a phase 1a/b study of OMP-131R10, a first-in-class anti-RSPO3 antibody, in advanced solid tumors and previously treated metastatic colorectal cancer (CRC). Eur J Cancer. 69(Suppl 1): S29–S30. 2016. View Article : Google Scholar
103	Le PN, McDermott JD and Jimeno A: Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28. Pharmacol Ther. 146:1–11. 2015. View Article : Google Scholar
104	Madan B, Ke Z, Harmston N, Ho SY, Frois AO, Alam J, Jeyaraj DA, Pendharkar V, Ghosh K, Virshup IH, et al: Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene. 35:2197–2207. 2016. View Article : Google Scholar
105	Chen CW, Beyer C, Liu J, Maier C, Li C, Trinh-Minh T, Xu X, Cole SH, Hsieh MH, Ng N, et al: Pharmacological inhibition of porcupine induces regression of experimental skin fibrosis by targeting Wnt signalling. Ann Rheum Dis. 76:773–778. 2017. View Article : Google Scholar : PubMed/NCBI
106	Blyszczuk P, Müller-Edenborn B, Valenta T, Osto E, Stellato M, Behnke S, Glatz K, Basler K, Lüscher TF, Distler O, et al: Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis. Eur Heart J. 38:1413–1425. 2017.
107	Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, Kasibhatla S, Schuller AG, Li AG, Cheng D, et al: Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA. 110:20224–20229. 2013. View Article : Google Scholar : PubMed/NCBI
108	Quackenbush KS, Bagby S, Tai WM, Messersmith WA, Schreiber A, Greene J, Kim J, Wang G, Purkey A, Pitts TM, et al: The novel tankyrase inhibitor (AZ1366) enhances irinotecan activity in tumors that exhibit elevated tankyrase and irinotecan resistance. Oncotarget. 7:28273–28285. 2016. View Article : Google Scholar : PubMed/NCBI
109	Lau T, Chan E, Callow M, Waaler J, Boggs J, Blake RA, Magnuson S, Sambrone A, Schutten M, Firestein R, et al: A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 73:3132–3144. 2013. View Article : Google Scholar : PubMed/NCBI
110	Shultz MD, Cheung AK, Kirby CA, Firestone B, Fan J, Chen CH, Chen Z, Chin DN, Dipietro L, Fazal A, et al: Identification of NVP-TNKS656: The use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. J Med Chem. 56:6495–6511. 2013. View Article : Google Scholar : PubMed/NCBI
111	Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, et al: Tankyrase inhibition stabilizes Axin and antagonizes Wnt signalling. Nature. 461:614–620. 2009. View Article : Google Scholar : PubMed/NCBI
112	Trautmann M, Sievers E, Aretz S, Kindler D, Michels S, Friedrichs N, Renner M, Kirfel J, Steiner S, Huss S, et al: SS18-SSX fusion protein-induced Wnt/β-catenin signaling is a therapeutic target in synovial sarcoma. Oncogene. 33:5006–5016. 2014. View Article : Google Scholar
113	Jang GB, Hong IS, Kim RJ, Lee SY, Park SJ, Lee ES, Park JH, Yun CH, Chung JU, Lee KJ, et al: Wnt/β-catenin small-molecule inhibitor CWP232228 preferentially inhibits the growth of breast cancer stem-like cells. Cancer Res. 75:1691–1702. 2015. View Article : Google Scholar : PubMed/NCBI
114	Yamada K, Hori Y, Yamaguchi A, Matsuki M, Tsukamoto S, Yokoi A, Semba T, Ozawa Y, Inoue S, Yamamoto Y, et al: Abstract 5177: E7386: First-in-class orally active CBP/β-catenin modulator as an anticancer agent. Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1–5; Washington, DC. Philadelphia. AACR; Cancer Res. 77(Suppl 13): 51772017. View Article : Google Scholar
115	Fang L, Zhu Q, Neuenschwander M, Specker E, Wulf-Goldenberg A, Weis WI, von Kries JP and Birchmeier W: A small-molecule antagonist of the β-catenin/TCF4 interaction blocks the self-renewal of cancer stem cells and suppresses tumorigenesis. Cancer Res. 76:891–901. 2016. View Article : Google Scholar
116	Zhou H, Mak PY, Mu H, Mak DH, Zeng Z, Cortes J, Liu Q, Andreeff M and Carter BZ: Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo. Leukemia. 31:2065–2074. 2017. View Article : Google Scholar : PubMed/NCBI
117	Katoh M and Katoh M: Identification and characterization of JMJD2 family genes in silico. Int J Oncol. 24:1623–1628. 2004.PubMed/NCBI
118	Berry WL and Janknecht R: KDM4/JMJD2 histone demethylases: Epigenetic regulators in cancer cells. Cancer Res. 73:2936–2942. 2013. View Article : Google Scholar : PubMed/NCBI
119	Kim TD, Fuchs JR, Schwartz E, Abdelhamid D, Etter J, Berry WL, Li C, Ihnat MA, Li PK and Janknecht R: Pro-growth role of the JMJD2C histone demethylase in HCT-116 colon cancer cells and identification of curcuminoids as JMJD2 inhibitors. Am J Transl Res. 6:236–247. 2014.PubMed/NCBI
120	Pedersen MT, Kooistra SM, Radzisheuskaya A, Laugesen A, Johansen JV, Hayward DG, Nilsson J, Agger K and Helin K: Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development. EMBO J. 35:1550–1564. 2016. View Article : Google Scholar : PubMed/NCBI
121	Tomaz RA, Harman JL, Karimlou D, Weavers L, Fritsch L, Bou-Kheir T, Bell E, Del Valle Torres I, Niakan KK, Fisher C, et al: Jmjd2c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation. Development. 144:567–579. 2017. View Article : Google Scholar : PubMed/NCBI
122	Lepourcelet M, Chen YN, France DS, Wang H, Crews P, Petersen F, Bruseo C, Wood AW and Shivdasani RA: Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex. Cancer Cell. 5:91–102. 2004. View Article : Google Scholar : PubMed/NCBI
123	Franci G, Sarno F, Nebbioso A and Altucci L: Identification and characterization of PKF118-310 as a KDM4A inhibitor. Epigenetics. 12:198–205. 2017. View Article : Google Scholar :
124	Wei W, Chua MS, Grepper S and So S: Small molecule antagonists of Tcf4/β-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int J Cancer. 126:2426–2436. 2010.
125	Hallett RM, Kondratyev MK, Giacomelli AO, Nixon AML, Girgis-Gabardo A, Ilieva D and Hassell JA: Small molecule antagonists of the Wnt/β-catenin signaling pathway target breast tumor-initiating cells in a Her2/Neu mouse model of breast cancer. PLoS One. 7:e339762012. View Article : Google Scholar
126	Beyer C, Reichert H, Akan H, Mallano T, Schramm A, Dees C, Palumbo-Zerr K, Lin NY, Distler A, Gelse K, et al: Blockade of canonical Wnt signalling ameliorates experimental dermal fibrosis. Ann Rheum Dis. 72:1255–1258. 2013. View Article : Google Scholar : PubMed/NCBI
127	Katoh M: Mutation spectra of histone methyltransferases with canonical SET domains and EZH2-targeted therapy. Epigenomics. 8:285–305. 2016. View Article : Google Scholar
128	Chen JF, Luo X, Xiang LS, Li HT, Zha L, Li N, He JM, Xie GF, Xie X and Liang HJ: EZH2 promotes colorectal cancer stem-like cell expansion by activating p21cip1-Wnt/β-catenin signaling. Oncotarget. 7:41540–41558. 2016.PubMed/NCBI
129	Huang M, Chen C, Geng J, Han D, Wang T, Xie T, Wang L, Wang Y, Wang C, Lei Z and Chu X: Targeting KDM1A attenuates Wnt/β-catenin signaling pathway to eliminate sorafenib-resistant stem-like cells in hepatocellular carcinoma. Cancer Lett. 398:12–21. 2017. View Article : Google Scholar : PubMed/NCBI
130	Jin Y, Zhou J, Xu F, Jin B, Cui L, Wang Y, Du X, Li J, Li P, Ren R and Pan J: Targeting methyltransferase PRMT5 eliminates leukemia stem cells in chronic myelogenous leukemia. J Clin Invest. 126:3961–3980. 2016. View Article : Google Scholar : PubMed/NCBI
131	Feinberg AP, Koldobskiy MA and Göndör A: Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet. 17:284–299. 2016. View Article : Google Scholar : PubMed/NCBI
132	Morera L, Lübbert M and Jung M: Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin Epigenetics. 8:572016. View Article : Google Scholar : PubMed/NCBI
133	Allis CD and Jenuwein T: The molecular hallmarks of epigenetic control. Nat Rev Genet. 17:487–500. 2016. View Article : Google Scholar : PubMed/NCBI
134	Jones PA, Issa JP and Baylin S: Targeting the cancer epigenome for therapy. Nat Rev Genet. 17:630–641. 2016. View Article : Google Scholar : PubMed/NCBI
135	Kim S, Xu X, Hecht A and Boyer TG: Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem. 281:14066–14075. 2006. View Article : Google Scholar : PubMed/NCBI
136	Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA and Young RA: Super-enhancers in the control of cell identity and disease. Cell. 155:934–947. 2013. View Article : Google Scholar : PubMed/NCBI
137	Yin JW and Wang G: The Mediator complex: A master coordinator of transcription and cell lineage development. Development. 141:977–987. 2014. View Article : Google Scholar : PubMed/NCBI
138	Mallinger A, Crumpler S, Pichowicz M, Waalboer D, Stubbs M, Adeniji-Popoola O, Wood B, Smith E, Thai C, Henley AT, et al: Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem. 58:1717–1735. 2015. View Article : Google Scholar : PubMed/NCBI
139	Dale T, Clarke PA, Esdar C, Waalboer D, Adeniji-Popoola O, Ortiz-Ruiz MJ, Mallinger A, Samant RS, Czodrowski P, Musil D, et al: A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol. 11:973–980. 2015. View Article : Google Scholar : PubMed/NCBI
140	Pelish HE, Liau BB, Nitulescu II, Tangpeerachaikul A, Poss ZC, Da Silva DH, Caruso BT, Arefolov A, Fadeyi O, Christie AL, et al: Mediator kinase inhibition further activates super-enhancer-associated genes in AML. Nature. 526:273–276. 2015. View Article : Google Scholar : PubMed/NCBI
141	Poss ZC, Ebmeier CC, Odell AT, Tangpeerachaikul A, Lee T, Pelish HE, Shair MD, Dowell RD, Old WM and Taatjes DJ: Identification of Mediator kinase substrates in human cells using cortistatin A and quantitative phosphoproteomics. Cell Rep. 15:436–450. 2016. View Article : Google Scholar : PubMed/NCBI
142	Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, Apuzzo T, Sperduti I, Volpe S, Cocorullo G, et al: CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 14:342–356. 2014. View Article : Google Scholar : PubMed/NCBI
143	Schmitt M, Metzger M, Gradl D, Davidson G and Orian-Rousseau V: CD44 functions in Wnt signaling by regulating LRP6 localization and activation. Cell Death Differ. 22:677–689. 2015. View Article : Google Scholar :
144	Jiang WG, Sanders AJ, Katoh M, Ungefroren H, Gieseler F, Prince M, Thompson SK, Zollo M, Spano D, Dhawan P, et al: Tissue invasion and metastasis: Molecular, biological and clinical perspectives. Semin Cancer Biol. 35(Suppl): S244–S275. 2015. View Article : Google Scholar : PubMed/NCBI
145	Hira VVV, Van Noorden CJF, Carraway HE, Maciejewski JP and Molenaar RJ: Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches. Biochim Biophys Acta. 1868:183–198. 2017.PubMed/NCBI
146	Vincan E, Flanagan DJ, Pouliot N, Brabletz T and Spaderna S: Variable FZD7 expression in colorectal cancers indicates regulation by the tumour microenvironment. Dev Dyn. 239:311–317. 2010.
147	Simmons GE Jr, Pandey S, Nedeljkovic-Kurepa A, Saxena M, Wang A and Pruitt K: Frizzled 7 expression is positively regulated by SIRT1 and β-catenin in breast cancer cells. PLoS One. 9:e988612014. View Article : Google Scholar
148	Qiu X, Jiao J, Li Y and Tian T: Overexpression of FZD7 promotes glioma cell proliferation by upregulating TAZ. Oncotarget. 7:85987–85999. 2016. View Article : Google Scholar : PubMed/NCBI
149	Carmon KS, Gong X, Yi J, Wu L, Thomas A, Moore CM, Masuho I, Timson DJ, Martemyanov KA and Liu QJ: LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells via the IQGAP1-Rac1 pathway. J Biol Chem. 292:14989–15001. 2017. View Article : Google Scholar : PubMed/NCBI
150	Ayyar BV, Arora S and O'Kennedy R: Coming-of-age of antibodies in cancer therapeutics. Trends Pharmacol Sci. 37:1009–1028. 2016. View Article : Google Scholar : PubMed/NCBI
151	Beck A, Goetsch L, Dumontet C and Corvaïa N: Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 16:315–337. 2017. View Article : Google Scholar : PubMed/NCBI
152	Kontermann RE and Brinkmann U: Bispecific antibodies. Drug Discov Today. 20:838–847. 2015. View Article : Google Scholar : PubMed/NCBI
153	Stadler CR, Bähr-Mahmud H, Celik L, Hebich B, Roth AS, Roth RP, Karikó K, Türeci O and Sahin Y: Elimination of large tumors in mice by mRNA-encoded bispecific antibodies. Nat Med. 23:815–817. 2017. View Article : Google Scholar : PubMed/NCBI
154	Jackson HJ, Rafiq S and Brentjens RJ: Driving CAR T-cells forward. Nat Rev Clin Oncol. 13:370–383. 2016. View Article : Google Scholar : PubMed/NCBI
155	Dai H, Wang Y, Lu X and Han W: Chimeric antigen receptors modified T-cells for cancer therapy. J Natl Cancer Inst. 108:djv4392016. View Article : Google Scholar : PubMed/NCBI
156	Casucci M, Nicolis di Robilant B, Falcone L, Camisa B, Norelli M, Genovese P, Gentner B, Gullotta F, Ponzoni M, Bernardi M, et al: CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood. 122:3461–3472. 2013. View Article : Google Scholar : PubMed/NCBI
157	Junttila MR, Mao W, Wang X, Wang BE, Pham T, Flygare J, Yu SF, Yee S, Goldenberg D, Fields C, et al: Targeting LGR5⁺ cells with an antibody-drug conjugate for the treatment of colon cancer. Sci Transl Med. 7:314ra1862015. View Article : Google Scholar
158	Gong X, Azhdarinia A, Ghosh SC, Xiong W, An Z, Liu Q and Carmon KS: LGR5-targeted antibody-drug conjugate eradicates gastrointestinal tumors and prevents recurrence. Mol Cancer Ther. 15:1580–1590. 2016. View Article : Google Scholar : PubMed/NCBI
159	Riechelmann H, Sauter A, Golze W, Hanft G, Schroen C, Hoermann K, Erhardt T and Gronau S: Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol. 44:823–829. 2008. View Article : Google Scholar : PubMed/NCBI
160	Al-Rawi V, Laeufer T, Glocker K, Heneka Y and Matzke-Ogi A: Abstract 4911: Allosteric inhibition of the receptor tyrosine kinases c-MET, RON and VEGFR-2 via the co-receptor CD44v6 by the novel compound AMC303. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; Apr 1-5, 2017; Washington, DC. Philadelphia. AACR; Cancer Res. 77(Suppl 13): 49112017. View Article : Google Scholar
161	Inglis DJ, Beaumont DM and Lavranos TC: Abstract 4695: Targeting the LGR5 complex with BNC101 to improve check- point inhibitor therapy in colorectal cancer. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; Apr 1-5, 2017; Washington, DC. Philadelphia. AACR; Cancer Res. 77(Suppl 13): 46952017. View Article : Google Scholar
162	Katoh M: The integration of genomics testing and functional proteomics in the era of personalized medicine. Expert Rev Proteomics. 14:1055–1058. 2017. View Article : Google Scholar : PubMed/NCBI
163	Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P, et al: Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 31:1023–1031. 2013. View Article : Google Scholar : PubMed/NCBI
164	Hovelson DH, McDaniel AS, Cani AK, Johnson B, Rhodes K, Williams PD, Bandla S, Bien G, Choppa P, Hyland F, et al: Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in solid tumors. Neoplasia. 17:385–399. 2015. View Article : Google Scholar : PubMed/NCBI
165	Friedman AA, Letai A, Fisher DE and Flaherty KT: Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 15:747–756. 2015. View Article : Google Scholar : PubMed/NCBI
166	Pauli C, Hopkins BD, Prandi D, Shaw R, Fedrizzi T, Sboner A, Sailer V, Augello M, Puca L, Rosati R, et al: Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 7:462–477. 2017. View Article : Google Scholar : PubMed/NCBI
167	Whorehouses D and Caldas C: Of mice and men: Patient-derived xenografts in cancer medicine. Ann Oncol. 28:2330–2331. 2017. View Article : Google Scholar
168	Singal AG and El-Serag HB: Hepatocellular carcinoma from epidemiology to prevention: Translating knowledge into practice. Clin Gastroenterol Hepatol. 13:2140–2151. 2015. View Article : Google Scholar : PubMed/NCBI
169	Zeng M, Mao XH, Li JX, Tong WD, Wang B, Zhang YJ, Guo G, Zhao ZJ, Li L, Wu DL, et al: Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 386:1457–1464. 2015. View Article : Google Scholar : PubMed/NCBI

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Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review)

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