ZEB1 is Negatively Correlated with E-Cadherin in Prostatic Anomaly Tissue

Sari Eka Pratiwi, Sri Nuryani Wahyuningrum, Rachmagreta Perdana Putri, Danarto Danarto, Didik Setyo Heriyanto, Nur Arfian, Sofia Mubarika Haryana, Indwiani Astuti

Abstract


Background: Prostatic anomalies are common in tumor or infection condition. The enlargement of prostate gland affects the epithelial cell polarity that involves epithelial-mesenchymal transition (EMT). Transition into mesenchymal is mediated by transcription factor ZEB1 and E-cadherin protein. Upregulation of ZEB1 and loss of E-Cadherin expression were associated to proliferation and metastasis of malignancy cells. This study aims to describe the correlation of ZEB1 and E-cadherin expression in prostatic anomaly.

Materials and method: Samples were Formalin Fixed Paraffin Embedded (FFPE) block consist of 8 block Benign Prostatic Hyperplasia (BPH), 6 blocks High Grade Prostatic Intraepithelial Neoplasia (HGPIN) and 6 blocks Prostate Carcinoma (PCA). The blocks then sliced into 5 sections to be prepared for RNA extraction procedures. ZEB1 and E-Cadherin expression was analyzed by semi-quantitative procedures using PCR and electrophoresis. Correlation between ZEB1 and E-Cadherin espression was analyzed using Spearman’s rank correlation.

Results: Relative expression of ZEB1 and E-cadherin mRNA in each group of prostatic anomaly were not significantly different (p>0.05). ZEB1 and E-Cadherin mRNA expression showed a significant and moderate level of negative correlation (p<0.05; 0.40 < r < 0.59). Increasing of ZEB1 mRNA expression will be followed by decreasing of E-Cadherin mRNA expression.

Conclusion: ZEB1 negatively correlates with E-cadherin due to EMT process in prostatic anomaly. High expression of ZEB1 induced down-regulation of E-cadherin and vise versa. Various studies can be developed, especially the development of targeted therapy against ZEB1 to suppress the EMT process by increasing the expression of E-cadherin.

Keywords: epithelial-mesenchymal transition (EMT), ZEB1, E-Cadherin, BPH, HGPIN, PCA


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References


Lee CH, Akin-Olugbade O, Kirschenbaum A. Overview of prostate anatomy, histology, and pathology. Endocrinol Metab Clin North Am. 2011; 40(3): 565-75, CrossRef.

Zhang SJ, Qian HN, Zhao Y, Sun K, Wang HQ, Liang GQ, et al. Relationship between age and prostate size. Asian J Androl. 2013; 15(1): 116-20, CrossRef.

Greco F, Inferrera A, La R, Navarra M, Casciaro M, Grosso G, et al. The potential role of micrornas as biomarkers in benign prostatic hyperplasia : a systematic review and meta-analysis. Eur Urol Focus. 2018; 5(3): 497-507, CrossRef.

Al-Dabbagh AA-D, Mohammad EJ, Jaffal WN. Is high grade prostatic intraepithelial neoplasia a risk factor for prostate cancer?— a local study. Open J Urol. 2018; 8(1): 81765, CrossRef.

Zynger DL, Yang X. High-grade prostatic intraepithelial neoplasia of the prostate : the precursor lesion of prostate cancer. Int J Clin Exp Pathol. 2009; 2(4): 327-38, article.

American Cancer Society [Internet]. Cancer Facts and Figures 2017 [cited 2022 Jul 30]. Available from: https://www.cancer.org/.

Komite Penanggulangan Kanker Nasional. Pedoman Nasional Pelayanan Kedokteran Kanker Paru. Jakarta: Kementrian Kesehatan RI; 2017, http://kanker.kemkes.go.id/.

Wong MCS, Goggins WB, Wang HHX, Fung FDH, Leung C, Wong SYS, et al. Global incidence and mortality for prostate cancer: analysis of temporal patterns and trends in 36 countries. Eur Urol. 2016; 70(5): 862-74, CrossRef.

Bashir MN. Epidemiology of prostate cancer. Asian Pac J Cancer Prev. 2015; 16(13): 5137-41, CrossRef.

Voss G, Haflidadóttir BS, Järemo H, Persson M, Catela Ivkovic T, Wikström P, et al. Regulation of cell-cell adhesion in prostate cancer cells by microRNA-96 through upregulation of E-Cadherin and EpCAM. Carcinogenesis. 2020; 41(7): 865-74, CrossRef.

Pasquier J, Abu-Kaoud N, Al Thani H, Rafii A. Epithelial to mesenchymal transition in a clinical perspective. J Oncol. 2015; 2015: 792182, CrossRef.

Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: Role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene. 2005; 24(50): 7443-54, CrossRef.

Kalluri R, Weinberg RA. Review series The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6): 1420-8, CrossRef.

Burton LJ, Hawsawi O, Loyd Q, Henderson V, Howard S, Harlemon M, et al. Association of epithelial mesenchymal transition with prostate and breast health disparities. PLoS One. 2018; 13(9): e0203855, CrossRef.

Tsoukalas N, Aravantinou-Fatorou E, Tolia M, Giaginis C, Galanopoulos M, Kiakou M, et al. Epithelial-mesenchymal transition in non small-cell lung cancer. Anticancer Res. 2017; 37(4): 1773-8, CrossRef.

Montanari M, Rossetti S, Cavaliere C, D’Aniello C, Malzone M, Vanacore D, et al. Epithelial-mesenchymal transition in prostate cancer: an overview. Oncotarget. 2017; 8(21): 35376-89, CrossRef.

Loboda A, Nebozhyn M V., Watters JW, Buser CA, Shaw PM, Huang PS, et al. EMT is the dominant program in human colon cancer. BMC Med Genomics. 2011; 4: 9, CrossRef.

Petrova YI, Schecterson L, Gumbiner BM. Roles for E-cadherin cell surface regulation in cancer. Mol Biol Cell. 2016; 27(21): 3233-44, CrossRef.

Sugihara T. Loss of adherens junction protein e-cadherin is a biomarker of high-grade histology and poor prognosis in endometrial cancer. Ann Clin Lab Res. 2016; 4(1): 1-5, CrossRef.

Fei Y, Liu XS, Wang F, Wang W, Liu SL. E-cadherin expression in normal and abnormal tissue specimens from patients with pancreatic carcinoma. Lab Med. 2010; 41(8): 473-7, CrossRef.

Repetto O, De Paoli P, De Re V, Canzonieri V, Cannizzaro R. Levels of soluble e-cadherin in breast, gastric, and colorectal cancers. Biomed Res Int. 2014; 2014: 408047, CrossRef.

Fonseca-Alves CE, Kobayashi PE, Leis-Filho AF, Lainetti P de F, Grieco V, Kuasne H, et al. E-cadherin downregulation is mediated by promoter methylation in canine prostate cancer. 2019; 10: 1242, CrossRef.

Aigner K, Dampier B, Descovich L, Mikula M, Sultan A, Schreiber M, et al. The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Oncogene. 2007; 26(49): 6979-88, CrossRef.

Zhang P, Sun Y, Ma L. ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 2015; 14(4): 481-7, CrossRef.

Ran J, Lin DL, Wu RF, Chen QH, Huang HP, Qiu NX, et al. ZEB1 promotes epithelial-mesenchymal transition in cervical cancer metastasis. Fertil Steril. 2015; 103(6): 1606-1614.e2, CrossRef.

Ma Y, Zheng X, Zhou J, Zhang Y, Chen K. ZEB1 promotes the progression and metastasis of cervical squamous cell carcinoma via the promotion of epithelial-mesenchymal transition. Int J Clin Exp Pathol. 2015; 8(9): 11258-67, article.

Drake J, Strohbehn G, Bair T, Moreland J, Henry M. ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells. Mol Biol Cell. 2009; 20(8): 2207-17, CrossRef.

Bery F, Figiel S, Kouba S, Fontaine D, Guéguinou M, Potier-Cartereau M, et al. Hypoxia promotes prostate cancer aggressiveness by upregulating EMT-activator Zeb1 and SK3 channel expression. Int J Mol Sci. 2020; 21(13): 4786, CrossRef.

Wong TS, Gao W, Chan JYW. Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors. Biomed Res Int. 2014; 2014: 921564, CrossRef.

Li F, Pascal LE, Stolz DB, Wang K, Zhou Y, Chen W, et al. E-cadherin is downregulated in benign prostatic hyperplasia and required for tight junction formation and permeability barrier in the prostatic epithelial cell monolayer. Prostate. 2019; 79(11): 1226-37, CrossRef.

Olson A, Le V, Aldahl J, Yu EJ, Hooker E, He Y, et al. The comprehensive role of E-cadherin in maintaining prostatic epithelial integrity during oncogenic transformation and tumor progression. PLoS Genet. 2019; 15(10): e1008451, CrossRef.

Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol. 2014; 15(3): 178-96, CrossRef.

Guilford P. E-cadherin downregulation in cancer: Fuel on the fire? Mol Med Today. 1999; 5(4): 172-7, CrossRef.

Xiong H, Hong J, Du W, Lin YW, Ren LL, Wang YC, et al. Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J Biol Chem. 2012; 287(8): 5819-32, CrossRef.

Graham TR, Zhau HE, Odero-Marah VA, Osunkoya AO, Kimbro KS, Tighiouart M, et al. Insulin-like growth factor-I - Dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 2008; 68(7): 2479-88, CrossRef.

Orellana‐Serradell O, Herrera D, Castellon E, Contreras H. The transcription factor ZEB1 promotes an aggressive phenotype in prostate cancer cell lines. Asian J Androl. 2018; 20(3): 294-9, CrossRef.

Drápela S, Bouchal J, Jolly MK, Culig Z, Souček K. ZEB1: A critical regulator of cell plasticity, dna damage response, and therapy resistance. Front Mol Biosci. 2020; 7: 36, CrossRef.

Loric S, Paradis V, Gala JL, Berteau P, Bedossa P, Benoit G, et al. Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer. Eur J Cancer. 2001; 37(12): 1475-81, CrossRef.




DOI: https://doi.org/10.21705/mcbs.v6i1.220

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