Skip to main content
Top
Published in: Clinical and Translational Oncology 7/2016

01-07-2016 | Research Article

Clinical significance of ECT2 expression in tissue and serum of gastric cancer patients

Authors: H.-B. Wang, H.-C. Yan, Y. Liu

Published in: Clinical and Translational Oncology | Issue 7/2016

Login to get access

Abstract

The ECT2 (epithelial cell transforming sequence 2) oncogene acted as a guanine nucleotide exchange factor for RhoGTPases, and regulates cytokinesis; thus, it may play a role in the pathogenesis of gastric cancer. In this study, we investigated the expression ECT2 gene in tissues and serum of gastric cancer patients to explore its clinical significance. ECT2 mRNA expression levels in tissues and serum were examined by RT-PCR, and ECT2 protein expression in tissue was evaluated by Western blot, and was further validated by immunohistochemistry and enzyme-linked immunosorbent assay at serum level. ECT2 level was significantly increased in the GC tissues and serum compared to normal control. ECT2 expression was positively correlated with the histologic differentiation, stages of TNM, and lymph node metastasis in GC (P < 0.05). Our results suggest that ECT2 plays an important role during GC progression and it may become a new diagnostic marker and therapeutic molecular target for management of GC.
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
2.
go back to reference Cuschieri SA, Hanna GB. Meta-analysis of D1 versus D2 gastrectomy for gastric adenocarcinoma: let us move on to another era. Ann Surg. 2014;259:e90.CrossRefPubMed Cuschieri SA, Hanna GB. Meta-analysis of D1 versus D2 gastrectomy for gastric adenocarcinoma: let us move on to another era. Ann Surg. 2014;259:e90.CrossRefPubMed
3.
go back to reference Grabsch HI, Tan P. Gastric cancer pathology and underlying molecular mechanisms. Dig Surg. 2013;30:150–8.CrossRefPubMed Grabsch HI, Tan P. Gastric cancer pathology and underlying molecular mechanisms. Dig Surg. 2013;30:150–8.CrossRefPubMed
4.
go back to reference Miki T, Smith CL, Long JE, Eva A, Fleming TP. Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature. 1993;362:462–5.CrossRefPubMed Miki T, Smith CL, Long JE, Eva A, Fleming TP. Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature. 1993;362:462–5.CrossRefPubMed
5.
go back to reference Matthews HK, Delabre U, Rohn JL, Guck J, Kunda P, Baum B. Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression. Dev Cell. 2012;23:371–83.CrossRefPubMedPubMedCentral Matthews HK, Delabre U, Rohn JL, Guck J, Kunda P, Baum B. Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression. Dev Cell. 2012;23:371–83.CrossRefPubMedPubMedCentral
7.
go back to reference Morita K, Hirono K, Han M. The Caenorhabditis elegans ect-2 RhoGEF gene regulates cytokinesis and migration of epidermal P cells. EMBO Rep. 2005;6:1163–8.CrossRefPubMedPubMedCentral Morita K, Hirono K, Han M. The Caenorhabditis elegans ect-2 RhoGEF gene regulates cytokinesis and migration of epidermal P cells. EMBO Rep. 2005;6:1163–8.CrossRefPubMedPubMedCentral
8.
go back to reference Kim JE, Billadeau DD, Chen J. The tandem BRCT domains of Ect2 are required for both negative and positive regulation of Ect2 in cytokinesis. J Biol Chem. 2005;280:5733–9.CrossRefPubMed Kim JE, Billadeau DD, Chen J. The tandem BRCT domains of Ect2 are required for both negative and positive regulation of Ect2 in cytokinesis. J Biol Chem. 2005;280:5733–9.CrossRefPubMed
10.
12.
go back to reference Justilien V, Jameison L, Der CJ, Rossman KL, Fields AP. Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation. J Biol Chem. 2011;286:8149–57.CrossRefPubMed Justilien V, Jameison L, Der CJ, Rossman KL, Fields AP. Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation. J Biol Chem. 2011;286:8149–57.CrossRefPubMed
13.
go back to reference Fields AP, Justilien V. The guanine nucleotide exchange factor (GEF) Ect2 is an oncogene in human cancer. Adv Enzyme Regul. 2010;50:190–200.CrossRefPubMed Fields AP, Justilien V. The guanine nucleotide exchange factor (GEF) Ect2 is an oncogene in human cancer. Adv Enzyme Regul. 2010;50:190–200.CrossRefPubMed
14.
go back to reference Murata Y, Minami Y, Iwakawa R, Yokota J, Usui S, Tsuta K, et al. ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma. Cancer Sci. 2014;105:490–7.CrossRefPubMedPubMedCentral Murata Y, Minami Y, Iwakawa R, Yokota J, Usui S, Tsuta K, et al. ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma. Cancer Sci. 2014;105:490–7.CrossRefPubMedPubMedCentral
15.
go back to reference Sano M, Genkai N, Yajima N, Tsuchiya N, Homma J, Tanaka R, et al. Expression level of ECT2 proto-oncogene correlates with prognosis in glioma patients. Oncol Rep. 2006;16:1093–8.PubMed Sano M, Genkai N, Yajima N, Tsuchiya N, Homma J, Tanaka R, et al. Expression level of ECT2 proto-oncogene correlates with prognosis in glioma patients. Oncol Rep. 2006;16:1093–8.PubMed
16.
go back to reference Chen J, Xia H, Zhang X, Karthik S, Pratap SV, Ooi LL, et al. ECT2 regulates the Rho/ERK signalling axis to promote early recurrence in human hepatocellular carcinoma. J Hepatol. 2015;62:1287–95.CrossRefPubMed Chen J, Xia H, Zhang X, Karthik S, Pratap SV, Ooi LL, et al. ECT2 regulates the Rho/ERK signalling axis to promote early recurrence in human hepatocellular carcinoma. J Hepatol. 2015;62:1287–95.CrossRefPubMed
17.
go back to reference Zhang ML, Lu S, Zhou L, Zheng SS. Correlation between ECT2 gene expression and methylation change of ECT2 promoter region in pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2008;7:533–8.PubMed Zhang ML, Lu S, Zhou L, Zheng SS. Correlation between ECT2 gene expression and methylation change of ECT2 promoter region in pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2008;7:533–8.PubMed
18.
go back to reference Wang YY, Ye ZY, Zhao ZS, Tao HQ, Li SG. Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer. J Cancer Res Clin Oncol. 2010;136:135–41.CrossRefPubMed Wang YY, Ye ZY, Zhao ZS, Tao HQ, Li SG. Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer. J Cancer Res Clin Oncol. 2010;136:135–41.CrossRefPubMed
19.
go back to reference Wang WF, Li J, Du LT, Wang LL, Yang YM, Liu YM, et al. Kruppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer. World J Gastroenterol. 2013;19:4309–15.CrossRefPubMedPubMedCentral Wang WF, Li J, Du LT, Wang LL, Yang YM, Liu YM, et al. Kruppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer. World J Gastroenterol. 2013;19:4309–15.CrossRefPubMedPubMedCentral
20.
go back to reference Sinha S, Yang W. Cellular signaling for activation of Rho GTPase Cdc42. Cell Signal. 2008;20:1927–34.CrossRefPubMed Sinha S, Yang W. Cellular signaling for activation of Rho GTPase Cdc42. Cell Signal. 2008;20:1927–34.CrossRefPubMed
21.
go back to reference Gomez del Pulgar T, Benitah SA, Valeron PF, Espina C, Lacal JC. Rho GTPase expression in tumourigenesis: evidence for a significant link. Bioessays. 2005;27:602–13.CrossRefPubMed Gomez del Pulgar T, Benitah SA, Valeron PF, Espina C, Lacal JC. Rho GTPase expression in tumourigenesis: evidence for a significant link. Bioessays. 2005;27:602–13.CrossRefPubMed
22.
go back to reference Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol. 2005;6:167–80.CrossRefPubMed Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol. 2005;6:167–80.CrossRefPubMed
23.
go back to reference Hirata D, Yamabuki T, Miki D, Ito T, Tsuchiya E, Fujita M, et al. Involvement of epithelial cell transforming sequence-2 oncoantigen in lung and esophageal cancer progression. Clin Cancer Res. 2009;15:256–66.CrossRefPubMed Hirata D, Yamabuki T, Miki D, Ito T, Tsuchiya E, Fujita M, et al. Involvement of epithelial cell transforming sequence-2 oncoantigen in lung and esophageal cancer progression. Clin Cancer Res. 2009;15:256–66.CrossRefPubMed
24.
go back to reference Salhia B, Tran NL, Chan A, Wolf A, Nakada M, Rutka F, et al. The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma. Am J Pathol. 2008;173:1828–38.CrossRefPubMedPubMedCentral Salhia B, Tran NL, Chan A, Wolf A, Nakada M, Rutka F, et al. The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma. Am J Pathol. 2008;173:1828–38.CrossRefPubMedPubMedCentral
25.
go back to reference Iyoda M, Kasamatsu A, Ishigami T, Nakashima D, Endo-Sakamoto Y, Ogawara K, et al. Epithelial cell transforming sequence 2 in human oral cancer. PLoS ONE. 2010;5:e14082.CrossRefPubMedPubMedCentral Iyoda M, Kasamatsu A, Ishigami T, Nakashima D, Endo-Sakamoto Y, Ogawara K, et al. Epithelial cell transforming sequence 2 in human oral cancer. PLoS ONE. 2010;5:e14082.CrossRefPubMedPubMedCentral
26.
go back to reference Spuul P, Ciufici P, Veillat V, Leclercq A, Daubon T, Kramer I, et al. Importance of RhoGTPases in formation, characteristics, and functions of invadosomes. Small GTPases. 2014;5:e28195.CrossRefPubMed Spuul P, Ciufici P, Veillat V, Leclercq A, Daubon T, Kramer I, et al. Importance of RhoGTPases in formation, characteristics, and functions of invadosomes. Small GTPases. 2014;5:e28195.CrossRefPubMed
27.
go back to reference Pectasides D, Mylonakis A, Kostopoulou M, Papadopoulou M, Triantafillis D, Varthalitis J, et al. CEA, CA 19-9, and CA-50 in monitoring gastric carcinoma. Am J Clin Oncol. 1997;20:348–53.CrossRefPubMed Pectasides D, Mylonakis A, Kostopoulou M, Papadopoulou M, Triantafillis D, Varthalitis J, et al. CEA, CA 19-9, and CA-50 in monitoring gastric carcinoma. Am J Clin Oncol. 1997;20:348–53.CrossRefPubMed
28.
go back to reference Watari J, Moriichi K, Tanabe H, Kashima S, Nomura Y, Fujiya M, et al. Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: an analysis of molecular pathology of Helicobacter pylori eradication. Int J Cancer. 2012;130:2349–58.CrossRefPubMed Watari J, Moriichi K, Tanabe H, Kashima S, Nomura Y, Fujiya M, et al. Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: an analysis of molecular pathology of Helicobacter pylori eradication. Int J Cancer. 2012;130:2349–58.CrossRefPubMed
Metadata
Title
Clinical significance of ECT2 expression in tissue and serum of gastric cancer patients
Authors
H.-B. Wang
H.-C. Yan
Y. Liu
Publication date
01-07-2016
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 7/2016
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1428-2

Other articles of this Issue 7/2016

Clinical and Translational Oncology 7/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine