Insight into the relationship between aryl-hydrocarbon receptor and β-catenin in human colon cancer cells


Autoři: Kazuhiro Shiizaki aff001;  Kenta Kido aff001;  Yasuhiro Mizuta aff001
Působiště autorů: Department of Applied Biosciences, Faculty of Life Sciences, Toyo University, Itakura-machi, Oura-gun, Gunma, Japan aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224613

Souhrn

β-Catenin is a multi-functional protein involved in cell adhesion and signal transduction and has a critical role in colorectal cancer development. β-Catenin positively regulates the aryl-hydrocarbon receptor (AhR) mediated signal by both induction of AhR expression and enhancement of AhR-dependent gene induction. Conversely, it was reported that AhR negatively regulates the β-catenin signal via ubiquitination and subsequent degradation in a ligand dependent manner. However, there have been conflicting data among previous studies regarding the relationship between these two proteins. In this report, we conducted confirmatory studies dissecting the relationship between AhR and β-catenin. We did not observe β-catenin degradation by AhR ligands in several colon cancer cell lines. Reporter assays revealed that the AhR ligand did not alter TcF/β-catenin dependent transcription. Yeast and mammalian two-hybrid assays failed to reconstruct the interaction of β-catenin and AhR even when other factors, Arnt, CUL4B, and DDB1, were co-expressed additionally. Independently to induction of AhR expression, β-catenin enhanced AhR-dependent transcriptional activation via the xenobiotic response element (XRE). Coimmunoprecipitation detected the formation of a β-catenin and ligand-activated AhR complex, which was thought to reflect the β-catenin mediated enhancement of the AhR signaling. Overall, we could only confirm unidirectional interaction, which is positive regulation of the AhR signal by β-catenin. These results suggested that data from previous reports on the degradation of β-catenin via liganded AhR warrants further investigation to yield clarity in the field.

Klíčová slova:

Co-immunoprecipitation – Colorectal cancer – DNA transcription – Luciferase – Plasmid construction – Transfection – Yeast two-hybrid assays – Reporter genes


Zdroje

1. MacDonald BT, Tamai K, He X. Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases. Dev Cell. 2009;17: 9–26. doi: 10.1016/j.devcel.2009.06.016 19619488

2. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303: 1483–1487. doi: 10.1126/science.1094291 15001769

3. Clevers H, Nusse R. Wnt/β-Catenin Signaling and Disease. Cell. 2012;149: 1192–1205. doi: 10.1016/j.cell.2012.05.012 22682243

4. van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111: 241–250. doi: 10.1016/s0092-8674(02)01014-0 12408868

5. Bersten DC, Sullivan AE, Peet DJ, Whitelaw ML. bHLH–PAS proteins in cancer. Nat Rev Cancer. 2013;13: 827–841. doi: 10.1038/nrc3621 24263188

6. Gu YZ, Hogenesch JB, Bradfield CA. The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol. 2000;40: 519–561. doi: 10.1146/annurev.pharmtox.40.1.519 10836146

7. Reyes H, Reisz-Porszasz S, Hankinson O. Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science. 1992;256: 1193–1195. doi: 10.1126/science.256.5060.1193 1317062

8. Denison MS, Fisher JM, Whitlock JP. Protein-DNA interactions at recognition sites for the dioxin-Ah receptor complex. J Biol Chem. 1989;264: 16478–16482. 2550446

9. Shimizu Y, Nakatsuru Y, Ichinose M, Takahashi Y, Kume H, Mimura J, et al. Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2000;97: 779–782. doi: 10.1073/pnas.97.2.779 10639156

10. Schneider AJ, Branam AM, Peterson RE. Intersection of AHR and Wnt signaling in development, health, and disease. Int J Mol Sci. 2014;15: 17852–17885. doi: 10.3390/ijms151017852 25286307

11. Chesire DR, Dunn TA, Ewing CM, Luo J, Isaacs WB. Identification of aryl hydrocarbon receptor as a putative Wnt/beta-catenin pathway target gene in prostate cancer cells. Cancer Res. 2004;64: 2523–2533. 15059908

12. 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: 239–248. doi: 10.1093/carcin/bgh298 15471898

13. Braeuning A, Köhle C, Buchmann A, Schwarz M. Coordinate regulation of cytochrome P450 1a1 expression in mouse liver by the aryl hydrocarbon receptor and the beta-catenin pathway. Toxicol Sci. 2011;122: 16–25. doi: 10.1093/toxsci/kfr080 21498875

14. Ohtake F, Baba A, Fujii-Kuriyama Y, Kato S. Intrinsic AhR function underlies cross-talk of dioxins with sex hormone signalings. Biochem Biophys Res Commun. 2008;370: 541–546. doi: 10.1016/j.bbrc.2008.03.054 18358233

15. Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, et al. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature. 2007;446: 562–566. doi: 10.1038/nature05683 17392787

16. Kawajiri K, Kobayashi Y, Ohtake F, Ikuta T, Matsushima Y, Mimura J, et al. Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+ mice with natural ligands. Proc Natl Acad Sci U S A 2009;106: 13481–13486. doi: 10.1073/pnas.0902132106 19651607

17. Metidji A, Omenetti S, Crotta S, Li Y, Nye E, Ross E, et al. The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining Intestinal Stem Cell Homeostasis and Barrier Integrity. Immunity. 2018;49: 353–362. doi: 10.1016/j.immuni.2018.07.010 30119997

18. Branam AM, Davis NM, Moore RW, Schneider AJ, Vezina CM, Peterson RE. TCDD Inhibition of Canonical Wnt Signaling Disrupts Prostatic Bud Formation in Mouse Urogenital Sinus. Toxicol Sci. 2013;133: 42–53. doi: 10.1093/toxsci/kft027 23429912

19. Wincent E, Stegeman JJ, Jönsson ME. Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions. Toxicol Appl Pharmacol. 2015;284: 163–179. doi: 10.1016/j.taap.2015.02.014 25711857

20. Procházková J, Kabátková M, Bryja V, Umannová L, Bernatík O, Kozubík A, et al. The interplay of the aryl hydrocarbon receptor and β-catenin alters both AhR-dependent transcription and Wnt/β-catenin signaling in liver progenitors. Toxicol Sci. 2011;122: 349–360. doi: 10.1093/toxsci/kfr129 21602191

21. Kasai S, Ishigaki T, Takumi R, Kamimura T, Kikuchi H. Beta-catenin signaling induces CYP1A1 expression by disrupting adherens junctions in Caco-2 human colon carcinoma cells. Biochim Biophys Acta. 2013;1830: 2509–2516. doi: 10.1016/j.bbagen.2012.11.007 23174221

22. Jin U-H, Lee S-O, Sridharan G, Lee K, Davidson LA, Jayaraman A, et al. Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Mol Pharmacol. 2014;85: 777–788. doi: 10.1124/mol.113.091165 24563545

23. Thaker AI, Rao MS, Bishnupuri KS, Kerr TA, Foster L, Marinshaw JM, et al. IDO1 Metabolites Activate β-catenin Signaling to Promote Cancer Cell Proliferation and Colon Tumorigenesis in Mice. Gastroenterology. 2013;145: 416–425. doi: 10.1053/j.gastro.2013.05.002 23669411

24. Park J-H, Lee J-M, Lee E-J, Kim D-J, Hwang W-B. Kynurenine promotes the goblet cell differentiation of HT-29 colon carcinoma cells by modulating Wnt, Notch and AhR signals. Oncol Rep. 2018;39: 1930–1938. doi: 10.3892/or.2018.6266 29436668

25. Shiizaki K, Ohsako S, Koyama T, Nagata R, Yonemoto J, Tohyama C. Lack of CYP1A1 expression is involved in unresponsiveness of the human hepatoma cell line SK-HEP-1 to dioxin. Toxicol Lett. 2005;160: 22–33. doi: 10.1016/j.toxlet.2005.06.003 16054781

26. Orford K, Crockett C, Jensen JP, Weissman AM, Byers SW. Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin. J Biol Chem. 1997;272: 24735–24738. doi: 10.1074/jbc.272.40.24735 9312064

27. Mimura J, Ema M, Sogawa K, Fujii-Kuriyama Y. Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev. 1999;13: 20–25. doi: 10.1101/gad.13.1.20 9887096

28. Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapić-Otrin V. The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A. Cancer Res. 2008;68: 5014–5022. doi: 10.1158/0008-5472.CAN-07-6162 18593899

29. Kumar MB, Perdew GH. Nuclear receptor coactivator SRC-1 interacts with the Q-rich subdomain of the AhR and modulates its transactivation potential. Gene Expr. 1999;8: 273–286. 10947077

30. Chen TR, Dorotinsky CS, McGuire LJ, Macy ML, Hay RJ. DLD-1 and HCT-15 cell lines derived separately from colorectal carcinomas have totally different chromosome changes but the same genetic origin. Cancer Genet Cytogenet. 1995;81: 103–108. doi: 10.1016/0165-4608(94)00225-z 7621404

31. Choi JD, Ryu M, Ae Park M, Jeong G, Lee J-S. FIP200 inhibits β-catenin-mediated transcription by promoting APC-independent β-catenin ubiquitination. Oncogene. 2013;32: 2421–2432. doi: 10.1038/onc.2012.262 22751121

32. Kaler P, Augenlicht L, Klampfer L. Activating mutations in β-catenin in colon cancer cells alter their interaction with macrophages; the role of snail. PLoS One. 2012;7: e45462. doi: 10.1371/journal.pone.0045462 23029025

33. Zou Y, Mi J, Cui J, Lu D, Zhang X, Guo C, et al. Characterization of nuclear localization signal in the N terminus of CUL4B and its essential role in cyclin E degradation and cell cycle progression. J Biol Chem. 2009;27; 284: 33320–33332.

34. Tripathi R, Kota SK, Srinivas UK. Cullin4B/E3-ubiquitin ligase negatively regulates beta-catenin. J Biosci. 2007;32: 1133–1138. doi: 10.1007/s12038-007-0114-0 17954973

35. Luecke-Johansson S, Gralla M, Rundqvist H, Ho JC, Johnson RS, Gradin K, et al. A Molecular Mechanism To Switch the Aryl Hydrocarbon Receptor from a Transcription Factor to an E3 Ubiquitin Ligase. Mol Cell Biol. 2017;37: e00630–16. doi: 10.1128/MCB.00630-16 28416634

36. Yuan J, Han B, Hu H, Qian Y, Liu Z, Wei Z, et al. CUL4B activates Wnt/β-catenin signalling in hepatocellular carcinoma by repressing Wnt antagonists. J Pathol. 2015;235: 784–795. doi: 10.1002/path.4492 25430888

37. He YM, Xiao YS, Wei L, Zhang JQ, Peng CH. CUL4B promotes metastasis and proliferation in pancreatic cancer cells by inducing epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. J Cell Biochem. 2018; 119:5308–5323. doi: 10.1002/jcb.26643 29274277

38. Song B, Zhan H, Bian Q, Li J. Knockdown of CUL4B inhibits proliferation and promotes apoptosis of colorectal cancer cells through suppressing the Wnt/β-catenin signaling pathway. Int J Clin Exp Pathol. 2015;8: 10394–10402. 26617747

39. Mao XW, Xiao JQ, Xu G, Li ZY, Wu HF, Li Y, Zheng YC, Zhang N. CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway. Oncotarget. 2017;8: 77241–77253. doi: 10.18632/oncotarget.20455 29100384

40. Ikuta T, Kobayashi Y, Kitazawa M, Shiizaki K, Itano N, Noda T, et al. ASC-associated inflammation promotes cecal tumorigenesis in aryl hydrocarbon receptor-deficient mice. Carcinogenesis. 2013;34: 1620–1627. doi: 10.1093/carcin/bgt083 23455376


Článek vyšel v časopise

PLOS One


2019 Číslo 11