Assessing E-Cadherin and Connexin 43 Gene Expressions in Colorectal Cancer

Year 2022, , 119 - 124, 31.12.2022

Saime Sürmen , Soykan Arıkan , Özlem Timirci Kahraman , Mustafa Gani Sürmen , Canan Cacına , İlhan Yaylım

https://doi.org/10.26650/experimed.1189327

Abstract

Objective: Dysregulation of cellular adhesion is one of the main mechanisms responsible for tumor initiation, proliferation, and survival. E-cadherin is a cell adhesion molecule associated with tissue invasion and metastasis in most epithelial cancers. Gap junctions are known as small molecular channels that allow communication between neighboring cells and consist of connexin molecules. Connexin 43 (Cx43) is a gap junction protein that plays a central role in cell-cycle regulation and has an important function in carcinogenesis. The present study aimed to evaluate the expression levels of E-cadherin and Cx43 in colorectal cancer patients using clinical and prognostic parameters.

Materials and Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) method was utilized to characterize the expression patterns of the E-cadherin and Cx43 genes in tumor and adjacent non-tumoral colon tissues from 32 colorectal cancer patients. Analysis of gene expression data was carried out using the delta-CT method.

Results: The results show the expression level of Cx43 to decrease 14-fold in tumor tissue compared to normal tissue (p<0.05). However, the study could find no significant difference with regard to E-cadherin expression.

Conclusion: The research provides valuable clues to the elucidation of tumor development and metastatic processes for further studies.

Keywords

Colorectal cancer, cell adhesion, connexin 43, E-cadherin, quantitative PCR

Supporting Institution

This study was supported by the Research Council of Istanbul University

Project Number

24522

References

• 1. Nalewajska M, Marchelek-Mysliwiec M, Opara-Bajerowicz M, Dziedziejko V, Pawlik A. Connexins-therapeutic targets in cancers. Int J Mol Sci 2020; 21(23): 9119. [CrossRef] google scholar
• 2. Bonacquisti EE and Nguyen J. Connexin 43 (Cx43) in cancer: Implications for therapeutic approaches via gap junctions. Cancer Lett 2019; 442: 439-44. [CrossRef] google scholar
• 3. Wu JI and Wang LH. Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application. J Biomed Sci 2019; 26(1): 8. [CrossRef] google scholar
• 4. Tang B, Peng ZH, Yu PW, Yu G, Qian F. Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes. Med Oncol 2011; 28(2): 502-8. [CrossRef] google scholar
• 5. Gall TM, Frampton AE. Gene of the month: E-cadherin (CDH1). J Clin Pathol 2013; 66(11): 928-32. [CrossRef] google scholar
• 6. Kaszak I, Witkowska-Pilaszewicz O, Niewiadomska Z, Dworecka-Kaszak B, Ngosa Toka F, Jurka P. Role of cadherins in cancer-A review. Int J Mol Sci 2020; 20: 7624. [CrossRef] google scholar
• 7. Techasen A, Loilome W, Namwat N, Khuntikeo N, Puapairoj A, Jearanaikoon P, Saya H, Yongvanit P. Loss of E-cadherin promotes migration and invasion of cholangiocarcinoma cells and serves as a potential marker of metastasis. Tumour Biol 2014; 35(9): 864552. [CrossRef] google scholar
• 8. Berx G, van Roy F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol 2009; 1(6): a003129. [CrossRef] google scholar
• 9. 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): e70858. [CrossRef] google scholar
• 10. Peng J, Qi S, Wang P, Li W, Song L, Liu C, et al. F. Meta-analysis of downregulated E-cadherin as a poor prognostic biomarker for cervical cancer. Future Oncol 2016; 12(5): 715-26. [CrossRef] google scholar
• 11. Shargh SA, Sakizli M, Khalaj V, Movafagh A, Yazdi H, Hagigatjou E, et al. Downregulation of E-cadherin expression in breast cancer by promoter hypermethylation and its relation with progression and prognosis of tumor. Med Oncol 2014; 31(11): 250. [CrossRef] google scholar
• 12. Xu HT, Li QC, Zhang YX, Zhao Y, Liu Y, Yang ZQ, et al. Connexin 43 recruits E-cadherin expression and inhibits the malignant behaviour of lung cancer cells. Folia Histochem Cytobiol 2008; 46(3): 315-21. [CrossRef] google scholar
• 13. Gassmann P, Haier J. The tumor cell-host organ interface in the early onset of metastatic organ colonisation. Clin Exp Metastasis 2008; 25(2): 171-81. [CrossRef] google scholar
• 14. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139(5): 871-90. [CrossRef] google scholar
• 15. Na TY, Schecterson L, Mendonsa AM, Gumbiner BM. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. Proc Natl Acad Sci USA. 2020; 117(11): 5931-37. [CrossRef] google scholar
• 16. Tsanou E, Peschos D, Batistatou A, Charalabopoulos A, Charalabopoulos K. The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Res 2008; 28(6A): 3815-26. google scholar
• 17. El-Bahrawy MA, Poulsom R, Jeffery R, Talbot I, Alison MR. The expression of E-cadherin and catenins in sporadic colorectal carcinoma. Hum Pathol 2001; 32(11): 1216-24. [CrossRef] google scholar
• 18. El-Bahrawy MA, Talbot IC, Poulsom R, Jeffery R, Alison MR. The expression of E-cadherin and catenins in colorectal tumours from familial adenomatous polyposis patients. J Pathol 2002; 198(1): 69-76. [CrossRef] google scholar
• 19. Palaghia M, Mihai C, Lozneanu L, Ciobanu D, Trofin AM, Rotariu A, et al. E-cadherin expression in primary colorectal cancer and metastatic lymph nodes. Rom J Morphol Embryol 2016; 57(1): 205-9. google scholar
• 20. Gao M, Zhang X, Li D, He P, Tian W, Zeng B. Expression analysis and clinical significance of eIF4E, VEGF-C, E-cadherin and MMP-2 in colorectal adenocarcinoma. Oncotarget 2016; 7(51): 85502-14. [CrossRef] google scholar
• 21. 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): e70858. [CrossRef] google scholar
• 22. Chakraborty S, Mitra S, Falk MM, Caplan SH, Wheelock MJ, Johnson KR, et al. E-cadherin differentially regulates the assembly of Connexin43 and Connexin32 into gap junctions in human squamous carcinoma cells. J Biol Chem 2010; 285(14):10761-76. [CrossRef] google scholar
• 23. Govindarajan R, Chakraborty S, Johnson KE, Falk MM, Wheelock MJ, Johnson KR, et al. Assembly of connexin43 into gap junctions is regulated differentially by E-cadherin and N-cadherin in rat liver epithelial cells. Mol Biol Cell 2010; 21(23): 4089-107. [CrossRef] google scholar
• 24. Kanczuga-Koda L, Wincewicz A, Fudala A, Abrycki T, Famulski W, Baltaziak M, et al. E-cadherin and ß-catenin adhesion proteins correlate positively with connexins in colorectal cancer. Oncol Lett 2014; 7(6): 1863-70. [CrossRef] google scholar
• 25. Zhao JQ, Sun FJ, Liu SS, Yang J, Wu YQ, Li GS, et al. Expression of connexin 43 and E-cadherin protein and mRNA in non-small cell lung cancers in Chinese patients. Asian Pac J Cancer Prev 2013; 14(2): 639-43. [CrossRef] google scholar
• 26. Sirnes S, Bruun J, Kolberg M, Kjenseth A, Lind GE, Svindland A, et al. Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer 2012; 131(3): 570-81. [CrossRef] google scholar
• 27. Ismail R, Rashid R, Andrabi K, Parray FQ, Besina S, Shah MA, et al. Pathological implications of Cx43 down-regulation in human colon cancer. Asian Pac J Cancer Prev 2014; 15(7): 2987-91. [CrossRef] google scholar