Abstract
Recently, studies have shown that Fucosylation plays an important role in the invasion and metastatic process of CSLCs. Understanding the expression pattern of fucosyltransferase (FUT) genes may help to suggest better-targeted therapy strategies for esophageal squamous cell carcinoma (ESCC). The study aimed to address the expression pattern of FUT gene variants in esophageal CSLCs and parental adherent cells. Sphere formation method was used to enrich CSLCs. Expression of FUT genes was examined in tumor sphere and parental adherent cells using the RT-PCR method and then relative expression of detected variants was performed by the Real-Time PCR method in both groups. The detected FUTs, also, were assessed in fresh ESCC tumors and the matched healthy controls. Analysis of The cell surface carbohydrate Lewis x (LeX, CD15) was performed by flow cytometry. Molecular analysis showed that the expression of FUT 3, 8 and POFUT1, 2 genes in tumorsphere were significantly higher than parental adherent cells. Analysis of fresh ESCC tumor tissues and the matched healthy controls showed that FUT8 and POFUT1, 2 genes in contrast to FUT 3 have higher expression in tumor tissues than controls. Flow cytometric analyses revealed that tumorsphere and their parent cells do not differ significantly in Lewis x surface marker. The present study showed that FUT 3, 8 and POFUT1, 2 genes upregulated in esophageal CSLCs in comparison to adherent cells. Understanding the expression pattern of FUT gene variants may help to suggest better-targeted therapy strategies for ESCC.
Similar content being viewed by others
References
Ayyoob, K., Masoud, K., Vahideh, K., Jahanbakhsh, A.: Authentication of newly established human esophageal squamous cell carcinoma cell line (YM-1) using short tandem repeat (STR) profiling method. Tumour Biol. 37, 3197–3204 (2016). https://doi.org/10.1007/s13277-015-4133-4
Baba, Y., Baba, H.: Gene-expression signature may be useful for the prediction of lymph node metastasis in esophageal cancer. Ann Transl Med. 6, 230 (2018)
Becker, D.J., Lowe, J.B.: Fucose: biosynthesis and biological function in mammals. Glycobiology. 13, 41r–53r (2003)
Blanas, A., Sahasrabudhe, N.M., Rodríguez, E., Van Kooyk, Y., Van Vliet, S.J.: Fucosylated antigens in Cancer: an Alliance toward tumor progression, metastasis, and resistance to chemotherapy. Front. Oncol. 8, 39–39 (2018)
Chatterjee, S.K., Bhattacharya, M., Barlow, J.J.: Glycosyltransferase and glycosidase activities in ovarian cancer patients. Cancer Res. 39, 1943–1951 (1979)
Chen, C.Y., Jan, Y.H., Juan, Y.H., Yang, C.J., Huang, M.S., Yu, C.J., Yang, P.C., Hsiao, M., Hsu, T.L., Wong, C.H.: Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer. Proc. Natl. Acad. Sci. U. S. A. 110, 630–635 (2013)
Dean, M., Fojo, T., Bates, S.: Tumour stem cells and drug resistance. Nat. Rev. Cancer. 5, 275–284 (2005)
Desiderio, V., Papagerakis, P., Tirino, V., Zheng, L., Matossian, M., Prince, M.E., Paino, F., Mele, L., Papaccio, F., Montella, R., Papaccio, G., Papagerakis, S.: Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells. Oncotarget. 6, 71–84 (2015)
Fan, J., Xie, T.P., Liu, Y.J., Hu, Y., Gu, T.J.: The expression of human alpha(1,3) Fucosyltransferase in human liver Cancer by in situ hybridization. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 28, 568–571 (1996)
Gholipour, M., Islami, F., Roshandel, G., Khoshnia, M., Badakhshan, A., Moradi, A., Malekzadeh, R.: Esophageal Cancer in Golestan Province, Iran: A review of genetic susceptibility and environmental risk factors. Middle East J Dig Dis. 8, 249–266 (2016)
Hirakawa, M., Takimoto, R., Tamura, F., Yoshida, M., Ono, M., Murase, K., Sato, Y., Osuga, T., Sato, T., Iyama, S., Miyanishi, K., Takada, K., Hayashi, T., Kobune, M., Kato, J.: Fucosylated TGF-beta receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells. Br. J. Cancer. 110, 156–163 (2014)
Hutchinson, W.L., Du, M.Q., Johnson, P.J., Williams, R.: Fucosyltransferases: differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis. Hepatology. 13, 683–688 (1991)
Ito, Y., Miyauchi, A., Yoshida, H., Uruno, T., Nakano, K., Takamura, Y., Miya, A., Kobayashi, K., Yokozawa, T., Matsuzuka, F., Taniguchi, N., Matsuura, N., Kuma, K., Miyoshi, E.: Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer Lett. 200, 167–172 (2003)
Jiang, Y., Liu, Z., Xu, F., Dong, X., Cheng, Y., Hu, Y., Gao, T., Liu, J., Yang, L., Jia, X., Qian, H., Wen, T., An, G.: Aberrant O-glycosylation contributes to tumorigenesis in human colorectal cancer. J. Cell. Mol. Med. 22, 4875–4885 (2018)
Lai, T.-Y., Chen, I.J., Lin, R.-J., Liao, G.-S., Yeo, H.-L., Ho, C.-L., Wu, J.-C., Chang, N.-C., Lee, A.C.-L., Yu, A.L.: Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells. Cell Death Dis. 5, 74–74 (2019)
Lao-Sirieix, P., Caldas, C., Fitzgerald, R.C.: Genetic predisposition to gastro-oesophageal cancer. Curr. Opin. Genet. Dev. 20, 210–217 (2010)
Leng, Q., Tsou, J.H., Zhan, M., Jiang, F.: Fucosylation genes as circulating biomarkers for lung cancer. J. Cancer Res. Clin. Oncol. 144, 2109–2115 (2018)
Liu, Y.C., Yen, H.Y., Chen, C.Y., Chen, C.H., Cheng, P.F., Juan, Y.H., Chen, C.H., Khoo, K.H., Yu, C.J., Yang, P.C., Hsu, T.L., Wong, C.H.: Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc. Natl. Acad. Sci. U. S. A. 108, 11332–11337 (2011)
Lowe, J.B.: Glycosylation in the control of selectin counter-receptor structure and function. Immunol. Rev. 186, 19–36 (2002)
Ma, B., Simala-Grant, J.L., Taylor, D.E.: Fucosylation in prokaryotes and eukaryotes. Glycobiology. 16, 158r–184r (2006)
Ma, L., Dong, P., Liu, L., Gao, Q., Duan, M., Zhang, S., Chen, S., Xue, R., Wang, X.: Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the notch signaling pathway. Biochem. Biophys. Res. Commun. 473, 503–510 (2016)
Mas, E., Pasqualini, E., Caillol, N., El Battari, A., Crotte, C., Lombardo, D., Sadoulet, M.O.: Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines. Glycobiology. 8, 605–613 (1998)
Mazo, I.B., Massberg, S., Von Andrian, U.H.: Hematopoietic stem and progenitor cell trafficking. Trends Immunol. 32, 493–503 (2011)
Miyoshi, E., Moriwaki, K., Nakagawa, T.: Biological function of fucosylation in cancer biology. J. Biochem. 143, 725–729 (2008)
Mondal, N., Dykstra, B., Lee, J., Ashline, D.J., Reinhold, V.N., Rossi, D.J., Sackstein, R.: Distinct human alpha(1,3)-fucosyltransferases drive Lewis-X/sialyl Lewis-X assembly in human cells. J. Biol. Chem. 293, 7300–7314 (2018)
Muinelo-Romay, L., Vazquez-Martin, C., Villar-Portela, S., Cuevas, E., Gil-Martin, E., Fernandez-Briera, A.: Expression and enzyme activity of alpha(1,6)fucosyltransferase in human colorectal cancer. Int. J. Cancer. 123, 641–646 (2008)
Narimatsu, H.: α3/4-Fucosyltransferase (FUT3, Lewis enzyme). In: Taniguchi, N., Honke, K., Fukuda, M., Clausen, H., Furukawa, K., Hart, G.W., Kannagi, R., Kawasaki, T., Kinoshita, T., Muramatsu, T., Saito, M., Shaper, J.H., Sugahara, K., Tabak, L.A., Van Den Eijnden, D.H., Yanagishita, M., Dennis, J.W., Furukawa, K., Hirabayashi, Y., Kawakita, M., Kimata, K., Lindahl, U., Narimatsu, H., Schachter, H., Stanley, P., Suzuki, A., Tsuji, S., Yamashita, K. (eds.) Handbook of Glycosyltransferases and Related Genes. Springer Japan, Tokyo (2002)
Nystrom, K., Grahn, A., Lindh, M., Brytting, M., Mandel, U., Larson, G., Olofsson, S.: Virus-induced transcriptional activation of host FUT genes associated with neo-expression of ley in cytomegalovirus-infected and sialyl-Lex in varicella-zoster virus-infected diploid human cells. Glycobiology. 17, 355–366 (2007)
Okajima, T., Irvine, K.D.: Regulation of notch signaling by o-linked fucose. Cell. 111, 893–904 (2002)
Padro, M., Cobler, L., Garrido, M., De Bolos, C.: Down-regulation of FUT3 and FUT5 by shRNA alters Lewis antigens expression and reduces the adhesion capacities of gastric cancer cells. Biochim. Biophys. Acta. 1810, 1141–1149 (2011)
Rappa, G., Mercapide, J., Anzanello, F., Prasmickaite, L., Xi, Y., Ju, J., Fodstad, O., Lorico, A.: Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets. Exp. Cell Res. 314, 2110–2122 (2008)
Saldova, R., Piccard, H., Perez-Garay, M., Harvey, D.J., Struwe, W.B., Galligan, M.C., Berghmans, N., Madden, S.F., Peracaula, R., Opdenakker, G., Rudd, P.M.: Increase in sialylation and branching in the mouse serum N-glycome correlates with inflammation and ovarian tumour progression. PLoS One. 8, e71159 (2013)
seidmann, L., Anspach, L., Roth, W.: The embryo-placental CD15-positive “vasculogenic zones” as a source of propranolol-sensitive pediatric vascular tumors. Placenta. 38, 93–99 (2016)
Singh, A., Settleman, J.: EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 29, 4741–4751 (2010)
Su, H., Hu, N., Yang, H.H., Wang, C., Takikita, M., Wang, Q.H., Giffen, C., Clifford, R., Hewitt, S.M., Shou, J.Z., Goldstein, A.M., Lee, M.P., Taylor, P.R.: Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin. Cancer Res. 17, 2955–2966 (2011)
Takahashi, M., Yokoe, S., Asahi, M., Lee, S.H., Li, W., Osumi, D., Miyoshi, E., Taniguchi, N.: N-glycan of ErbB family plays a crucial role in dimer formation and tumor promotion. Biochim. Biophys. Acta. 1780, 520–524 (2008)
Tirino, V., Desiderio, V., Paino, F., Papaccio, G., De Rosa, M.: Methods for cancer stem cell detection and isolation. Methods Mol. Biol. 879, 513–529 (2012)
Vajaria, B.N., Patel, P.S.: Glycosylation: a hallmark of cancer? Glycoconj. J. 34, 147–156 (2017)
Wang, X., Gu, J., Ihara, H., Miyoshi, E., Honke, K., Taniguchi, N.: Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling. J. Biol. Chem. 281, 2572–2577 (2006)
Wang, X., Chen, J., Li, Q.K., Peskoe, S.B., Zhang, B., Choi, C., Platz, E.A., Zhang, H.: Overexpression of α (1,6) fucosyltransferase associated with aggressive prostate cancer. Glycobiology. 24, 935–944 (2014)
Yakubu, R.R., Weiss, L.M., Silmon De Monerri, N.C.: Post-translational modifications as key regulators of apicomplexan biology: insights from proteome-wide studies. Mol. Microbiol. 107, 1–23 (2018)
Yang, X., Liu, S., Yan, Q.: Role of fucosyltransferase IV in epithelial-mesenchymal transition in breast cancer cells. Cell Death Dis. 4, e735 (2013)
Yu, C. C., Lo, W. L., Chen, Y. W., Huang, P. I., Hsu, H. S., Tseng, L. M., Hung, S. C., Kao, S. Y., Chang, C. J. & Chiou, S. H.. Bmi-1 regulates snail expression and promotes metastasis ability in head and neck squamous Cancer-derived ALDH1 positive cells. J Oncol, 2011 (2011)
Zhang, Z., Wuhrer, M., Holst, S.: Serum sialylation changes in cancer. Glycoconj. J. 35, 139–160 (2018)
Zhao, Y.P., Xu, X.Y., Fang, M., Wang, H., You, Q., Yi, C.H., Ji, J., Gu, X., Zhou, P.T., Cheng, C., Gao, C.F.: Decreased core-fucosylation contributes to malignancy in gastric cancer. PLoS One. 9, e94536 (2014)
Acknowledgments
We thank Dr. Masoud khoshnia for providing ESCC and normal samples, and Dr. seyed Mehdi Jafari for editing the manuscript. Special thanks to the patients with esophageal cancer who participated in this study. This work was supported by the Golestan University of Medical Sciences (research grant number: 970308034).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sadeghzadeh, Z., Khosravi, A., Jazi, M.S. et al. Upregulation of Fucosyltransferase 3, 8 and protein O-Fucosyltransferase 1, 2 genes in esophageal cancer stem-like cells (CSLCs). Glycoconj J 37, 319–327 (2020). https://doi.org/10.1007/s10719-020-09917-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-020-09917-z