Differences in the Expression of β-Catenin Nucleus/Cytoplasm Ratio e-Cadherin and n-Cadherin and Correlation of β-Catenin Cytoplasm and Cadherin in Model of Duke D Stage Colorectal Cancer Cell Line
DOI:
https://doi.org/10.3889/oamjms.2021.6140Keywords:
β-catenin, Colorectal cancer, E-cadherin, Fluorescein-5-isothiocyanate staining, N-cadherinAbstract
BACKGROUND: β-catenin has a critical role in the homeostasis processes. Wnt/β-catenin signaling mainly involved in the modulation of cancer cell development.
AIM: This research aimed to investigate the differences of β-catenin expression observed in the form of nucleus–cytoplasm ratio, the differences of E-cadherin and N-cadherin expressions, and the correlation between N-cadherin and E-cadherin and β-catenin cytoplasm in Dukes D stage colorectal cancer (CRC), which is an advanced stage and has experienced metastasis.
MATERIALS AND METHODS: This study followed an experimental research design. The processes of culture manufacturing and subculture preparation of Dukes D stage CRC cell line model were performed before the administration of β-catenin, E-cadherin, and N-cadherin antibodies. The next process was staining using fluorescein-5-isothiocyanate and rhodamine, and observations were performed using a confocal microscope. The number of cells was counted, and the intensity of antibody expression based on the arbitrary unit was measured.
RESULTS: There was a significant difference between the expression of β-catenin nucleus and cytoplasm expression (p = 0.00), as well as between E-cadherin expression and N-cadherin expression (p = 0.00). In addition, a correlation also existed between an increased N-cadherin expression and decreased E-cadherin expression and β-catenin cytoplasm in Dukes D stage CRC, but the results were not significant (p = 0.837 and p = 0.108).
CONCLUSION: In advanced-stage CRC (Dukes D), the Wnt signaling proved to be active and was characterized by a high expression of β-catenin nucleus, it activates the target gene. Similarly, at the Dukes D stage, N-cadherin expression increased whereas E-cadherin expression decreased in which causing the translocation of β-catenin into the nucleus.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Zarkavelis G, Buossios S, Papadaki A, Katsanos KH, Chistodoulou DK, Pentheroudakis G. Current and future biomarkers in colorectal cancer. Ann Gastroenterol. 2017;30(6):613-21. PMid:29118555
Palaghia M, Mihai C, Lozneanu L, Ciobanu D, Trofin AM, Rotario A, et al. E-cadherin expression in primary colorectal cancer and metastatic lymph nodes. Rom J Morphol Embryol. 2016;57(1):205-9. PMid:27151709
Ahmad A, Stromberg VH. Expression of β-catenin and e-cadherin, their clinical significance and association with complexity and index of colon carcinoma. Adv Genet Eng. 2016;5(3):1-10. https://doi.org/10.4172/2169-0111.1000156 DOI: https://doi.org/10.4172/2169-0111.1000156
Akkoca AN, Yanik S, Ozdemir ZT, Cihan FG, Sayar S, Cincin G, et al. TNM and modified dukes staging along with the demographic characteristics of patients with colorectal carcinoma. Int J Clin Exp Med. 2014;7(9):2828-35. PMid:25356145
Saltz LB. Colorectal Cancer: Evidence-based Chemotherapy Strategies. Totowa, New Jersey: Humana Press; 2007.
Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: An overview. Cancers. 2014;6(3):1769-92. https://doi.org/10.3390/cancers6031769 PMid:25198391 DOI: https://doi.org/10.3390/cancers6031769
Colussi D, Brandi G, Bazzoli F, Ricciardiello L. Molecular pathways involved in colorectal cancer: Implications for disease behavior and prevention. Int J Mol Sci. 2013;14(8):16365-85. https://doi.org/10.3390/ijms140816365 PMid:23965959 DOI: https://doi.org/10.3390/ijms140816365
Xu Y, Pasche B. TGF-β signaling alterations and susceptibility to colorectal cancer. Hum Mol Genet. 2007;16:14-20. PMid:17613544 DOI: https://doi.org/10.1093/hmg/ddl486
Polimeno L, Barone M, Mosca A, Viggiani MT, Joukar F, Mansour- Ghanaei F, et al. Soy metabolism by gut microbiota from patients with precancerous intestinal lesions. Microorganism. 2020;8(4):469. https://doi.org/10.3390/microorganisms8040469 PMid:32218321 DOI: https://doi.org/10.3390/microorganisms8040469
Shang S, Hua F, Hu ZW. The regulation of β-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget. 2017;8(20):33972-89. https://doi.org/10.18632/oncotarget.15687 PMid:28430641 DOI: https://doi.org/10.18632/oncotarget.15687
Menezes ME. The Wnt/β-catenin signaling pathway in epithelial mesenchymal transition. Post Doc J. 2014;2(7):1-9. DOI: https://doi.org/10.14304/SURYA.JPR.V2N7.1
Chen J, Xie ZR, Wu Y. Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway. PLoS One. 2014;9(6):1-12. https://doi.org/10.1371/journal.pone.0100702 DOI: https://doi.org/10.1371/journal.pone.0100702
Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J Cell Sci. 2007;121(6):727-35. https://doi.org/10.1242/jcs.000455 PMid:18322269 DOI: https://doi.org/10.1242/jcs.000455
Heuberger J, Birchmeier W. Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling. Cold Spring Harb Perspect Biol. 2010;2(2):a002915. https://doi.org/10.1101/cshperspect.a002915 PMid:20182623 DOI: https://doi.org/10.1101/cshperspect.a002915
Ioannou M, Kouravas E, Papamichali R, Samara M, Chiotoglou I. Smad4 and epithelial-mesenchymal transition protein in colorectal carcinoma: An immunohistochemical study. J Mol Histol. 2018;49(3):235-44. https://doi.org/10.1007/s10735-018-9763-6 PMid:29468299 DOI: https://doi.org/10.1007/s10735-018-9763-6
Loh C, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, et al. The e-cadherin and n-cadherin switch in epithelial to mesenchymal transition: Signaling, therapeutic implications, and challenges. Cells. 2019;8(10):1-33. https://doi.org/10.3390/cells8101118 PMid:31547193 DOI: https://doi.org/10.3390/cells8101118
National Cancer Intelligence Network. Colorectal Cancer Survival by Stage; 2010. Available from: http://www.ncin.orguk/databriefing. [Last accessed on 2021 Feb 26].
Ueno H, Price AB, Path FR, Wilkinson KH, Jass JR, Talbot IC. A new prognostic staging system for rectal cancer. Ann Surg. 2004;240(5):832-9. https://doi.org/10.1097/01.sla.0000143243.81014.f2 PMid:15492565 DOI: https://doi.org/10.1097/01.sla.0000143243.81014.f2
Gao Z, Lu C, Wang M, Han Y, Guo L. Differential β-catenin expression levels are associated with morphological features and prognosis of colorectal cancer. Oncol Lett. 2014;8(5):2069- 76. https://doi.org/10.3892/ol.2014.2433 PMid:25295092 DOI: https://doi.org/10.3892/ol.2014.2433
Yoshida N, Kinugasa T, Ohshima K, Yuge K, Ohchi T, Fujino S, et al. Analysis of Wnt and β-catenin expression in advanced colorectal cancer. Anticancer Res. 2015;35(8):4403-10. PMid:26168479
Ye Z, Zhou M, Tian B, Wu B, Li Z. Expression of IncRNA-CCAT1, E-cadherin and N-cadherin in colorectal cancer and its significance. Int J Clin Exp Med. 2015;8(3):3707-15. PMid:26064266
Kim SA, Inamura K, Yamauchi M, Nishihara R, Mima K, Sukawa Y, et al. Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumor growth and lymph node metastasis. Br J Cancer. 2016;114(2):199-206. https://doi.org/10.1038/bjc.2015.347 PMid:26742007 DOI: https://doi.org/10.1038/bjc.2015.347
He X, Chen Z, Jia M, Zhao X. Downregulated e-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: Evidence from meta-analysis. PLoS One. 2013;8(7):1-8. https://doi.org/10.1371/journal.pone.0070858 PMid:23923027 DOI: https://doi.org/10.1371/journal.pone.0070858
Li W, Xiao D, Wu H, Xu L. The epithelial cadherin-160C/A polymorphism is associated with decreased risk of colorectal cancer: A case-caontrol study. Clin Exp Med. 2020;20(1):73-8. https://doi.org/10.1007/s10238-019-00586-3 PMid:31625007 DOI: https://doi.org/10.1007/s10238-019-00586-3
Sun N, Chen J, Hu G, Chen X, Jiang J, Zhang L, et al. Association between the epithelial cadherin-160C/A polymorphism and colorectal cancer risk: Evidence from a meta-analysis. Crit Rev Eukaryot Gene Expr. 2017;27(4):347-54. https://doi.org/10.1615/critreveukaryotgeneexpr.2017020525 PMid:29283329 DOI: https://doi.org/10.1615/CritRevEukaryotGeneExpr.2017020525
Zhu S, Zhao G, Zhao X, Zhan X, Cai M, Geng C, et al. Elevated soluble E-cadherin during the epithelial-mesenchymal transition process and as a diagnostic marker in colorectal cancer. Gene. 2020;754:144899. https://doi.org/10.1016/j.gene.2020.144899 PMid:32544494 DOI: https://doi.org/10.1016/j.gene.2020.144899
Chen Z, He X, Jia M, Liu Y, Qu D, Wu D, et al. β-catenin overexpression in the nucleus predicts progress disease and unfavourable survival in colorectal cancer: A meta-analysis. PLoS One. 2013;8(5):1-10. https://doi.org/10.1371/journal.pone.0063854 PMid:23717499 DOI: https://doi.org/10.1371/journal.pone.0063854
Wang T, Lin F, Sun X, Jiang L, Mao R, Zhou S, et al. HOXB8 enhances the proliferation and metastasis of colorectal cancer Cells by promoting EMT via STAT3 activation. Cancer Cell Int. 2019;3(19):3. https://doi.org/10.1186/s12935-018-0717-6 PMid:30622439 DOI: https://doi.org/10.1186/s12935-018-0717-6
Polimeno L, Francavilla A, Piscitelli D, Fiore MG, Polimeno R, Topi S, et al. The role of PIAS3, p-STAT3 and ALR in colorectal cancer: New translational molecular features for and old disease. Eur Rev Pharmacol Sci. 2020;24(20):10496-511. https://doi.org/10.1016/s1590-8658(09)60309-1 PMid:33155205 DOI: https://doi.org/10.1016/S1590-8658(09)60309-1
Sameri S, Saidijam M, Bahreini F, Najafi R. Cancer chemopreventive activities of silibinin on colorectal cancer through regulation of E-cadherin/β-catenin pathway. Nutr Cancer. 2020;4:1-11. https://doi.org/10.1080/01635581.2020.1800764 PMid:32748663658 DOI: https://doi.org/10.1080/01635581.2020.1800764
Downloads
Published
How to Cite
License
Copyright (c) 2020 Winarko Winarko, Pudji Rahayu, Djoko Soeatmadji, Karyono Mintaroem (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0