Skip to main content
Top
Published in: Tumor Biology 2/2014

01-02-2014 | Research Article

Inhibition of gastric cancer cell growth and invasion through siRNA-mediated knockdown of guanine nucleotide exchange factor Vav3

Authors: Bibo Tan, Yong Li, Qun Zhao, Liqiao Fan, Dong Wang, Yü Liu

Published in: Tumor Biology | Issue 2/2014

Login to get access

Abstract

Vav3, a Rho GTPase guanine nucleotide exchange factor, is associated with tumor growth, apoptosis, invasion and metastasis, and angiogenesis. However, the role of Vav3 in gastric cancer remains unclear. In this study, Vav3 expression was blocked by specific siRNA in gastric cancer cell line MGC803. MTT was used to assay cell proliferation activity; wound healing assay and transwell assay were applied to detect cell migration and invasion ability; and qRT-PCR and Western blot were employed to detect expression levels of Vav3 as well as proliferation, migration, and invasion-related genes. The results showed that Vav3 expression in gastric cancer tissues and cell lines was significantly upregulated and was higher than that in adjacent tissues of cancer and normal gastric mucosal cell lines. Vav3 knockdown inhibited proliferation, migration, and invasion of MGC803 gastric cancer cells. The expression of P21, P27, TIMP-1, and TIMP-2 was upregulated, while proliferating cell nuclear antigen, cyclin E1, matrix metalloproteinase (MMP)-2, and MMP-7 were downregulated by Vav3 knockdown in MGC803 gastric cells. In conclusion, Vav3 is involved in the proliferation, migration, and invasion of gastric cancer cell as a tumor oncogene.
Literature
1.
go back to reference Lee JH, Choi MG, Min BH, Noh JH, Sohn TS, Bae JM, et al. Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer. Br J Surg. 2012;99:1688–92.PubMedCrossRef Lee JH, Choi MG, Min BH, Noh JH, Sohn TS, Bae JM, et al. Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer. Br J Surg. 2012;99:1688–92.PubMedCrossRef
2.
go back to reference Choi JH, Shin NR, Moon HJ, Kwon CH, Kim GH, Song GA, et al. Identification of S100A8 and S100A9 as negative regulators for lymph node metastasis of gastric adenocarcinoma. Histol Histopathol. 2012;27:1439–48.PubMed Choi JH, Shin NR, Moon HJ, Kwon CH, Kim GH, Song GA, et al. Identification of S100A8 and S100A9 as negative regulators for lymph node metastasis of gastric adenocarcinoma. Histol Histopathol. 2012;27:1439–48.PubMed
3.
go back to reference Zhu ZL, Yan BY, Zhang Y, Yang YH, Wang ZM, Zhang HZ, et al. PINCH expression and its clinicopathological significance in gastric adenocarcinoma. Dis Markers. 2012;33:171–8.PubMedCentralPubMedCrossRef Zhu ZL, Yan BY, Zhang Y, Yang YH, Wang ZM, Zhang HZ, et al. PINCH expression and its clinicopathological significance in gastric adenocarcinoma. Dis Markers. 2012;33:171–8.PubMedCentralPubMedCrossRef
4.
go back to reference Chen P, Zhao D, Sun Y, Huang L, Zhang S, Yuan Y. Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue and involved in cell metastasis. Oncol Rep. 2012;28:2149–55.PubMed Chen P, Zhao D, Sun Y, Huang L, Zhang S, Yuan Y. Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue and involved in cell metastasis. Oncol Rep. 2012;28:2149–55.PubMed
5.
go back to reference Wu Q, Jin H, Yang Z, Luo G, Lu Y, Li K, et al. MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochem Biophys Res Commun. 2010;392:340–5.PubMedCrossRef Wu Q, Jin H, Yang Z, Luo G, Lu Y, Li K, et al. MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochem Biophys Res Commun. 2010;392:340–5.PubMedCrossRef
6.
go back to reference Ma PF, Chen JQ, Wang Z, Liu JL, Li BP. Function of chloride intracellular channel 1 in gastric cancer cells. World J Gastroenterol. 2012;18:3070–80.PubMedCrossRef Ma PF, Chen JQ, Wang Z, Liu JL, Li BP. Function of chloride intracellular channel 1 in gastric cancer cells. World J Gastroenterol. 2012;18:3070–80.PubMedCrossRef
7.
go back to reference Kundu J, Wahab SM, Kundu JK, Choi YL, Erkin OC, Lee HS, et al. Tob1 induces apoptosis and inhibits proliferation, migration and invasion of gastric cancer cells by activating Smad4 and inhibiting β‑catenin signaling. Int J Oncol. 2012;41:839–48.PubMed Kundu J, Wahab SM, Kundu JK, Choi YL, Erkin OC, Lee HS, et al. Tob1 induces apoptosis and inhibits proliferation, migration and invasion of gastric cancer cells by activating Smad4 and inhibiting β‑catenin signaling. Int J Oncol. 2012;41:839–48.PubMed
8.
go back to reference Zhang J, Zhu JS, Zhou Z, Chen WX, Chen NW. Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo. Oncol Rep. 2012;27:1511–9.PubMed Zhang J, Zhu JS, Zhou Z, Chen WX, Chen NW. Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo. Oncol Rep. 2012;27:1511–9.PubMed
9.
go back to reference Sun ZH, Bu P. Downregulation of phosphatase of regenerating liver-3 is involved in the inhibition of proliferation and apoptosis induced by emodin in the SGC-7901 human gastric carcinoma cell line. Exp Ther Med. 2012;3:1077–81.PubMedCentralPubMed Sun ZH, Bu P. Downregulation of phosphatase of regenerating liver-3 is involved in the inhibition of proliferation and apoptosis induced by emodin in the SGC-7901 human gastric carcinoma cell line. Exp Ther Med. 2012;3:1077–81.PubMedCentralPubMed
10.
go back to reference Fernandez-Salguero PM. A remarkable new target gene for the dioxin receptor: the Vav3 proto-oncogene links AhR to adhesion and migration. Cell Adhes Migr. 2010;4:172–5.CrossRef Fernandez-Salguero PM. A remarkable new target gene for the dioxin receptor: the Vav3 proto-oncogene links AhR to adhesion and migration. Cell Adhes Migr. 2010;4:172–5.CrossRef
11.
go back to reference Liu Y, Wu X, Dong Z, Lu S. The molecular mechanism of Vav3 oncogene on upregulation of androgen receptor activity in prostate cancer cells. Int J Oncol. 2010;36:623–33.PubMedCrossRef Liu Y, Wu X, Dong Z, Lu S. The molecular mechanism of Vav3 oncogene on upregulation of androgen receptor activity in prostate cancer cells. Int J Oncol. 2010;36:623–33.PubMedCrossRef
12.
go back to reference Travert M, Huang Y, de Leval L, Martin-Garcia N, Delfau-Larue MH, Berger F, et al. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. Blood. 2012;119:5795–806.PubMedCentralPubMedCrossRef Travert M, Huang Y, de Leval L, Martin-Garcia N, Delfau-Larue MH, Berger F, et al. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. Blood. 2012;119:5795–806.PubMedCentralPubMedCrossRef
13.
go back to reference Lee K, Liu Y, Mo JQ, Zhang J, Dong Z, Lu S. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer. BMC Cancer. 2008;8:158.PubMedCentralPubMedCrossRef Lee K, Liu Y, Mo JQ, Zhang J, Dong Z, Lu S. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer. BMC Cancer. 2008;8:158.PubMedCentralPubMedCrossRef
14.
go back to reference Lin KY, Wang LH, Hseu YC, Fang CL, Yang HL, Kumar KJ, et al. Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. Mol Cancer Res. 2012;10:750–9.PubMedCrossRef Lin KY, Wang LH, Hseu YC, Fang CL, Yang HL, Kumar KJ, et al. Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. Mol Cancer Res. 2012;10:750–9.PubMedCrossRef
15.
go back to reference Zheng KC, Aoki K, Li XQ, Lin SG, Wu BS, Zhong WL, et al. Serum pepsinogens, gastrin-17 and Helicobacter pylori antibody in the residents of two cities in china with distinct mortality rates of gastric cancer. Tohoku J Exp Med. 2012;228:289–94.PubMedCrossRef Zheng KC, Aoki K, Li XQ, Lin SG, Wu BS, Zhong WL, et al. Serum pepsinogens, gastrin-17 and Helicobacter pylori antibody in the residents of two cities in china with distinct mortality rates of gastric cancer. Tohoku J Exp Med. 2012;228:289–94.PubMedCrossRef
16.
go back to reference Wang HM, Huang CM, Zheng CH, Li P, Xie JW, Wang JB, et al. Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach. World J Gastroenterol. 2012;18:5470–5.PubMedCrossRef Wang HM, Huang CM, Zheng CH, Li P, Xie JW, Wang JB, et al. Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach. World J Gastroenterol. 2012;18:5470–5.PubMedCrossRef
17.
go back to reference Dong Z, Liu Y, Levin L, Oleksowicz L, Wang J, Lu S. Vav3 oncogene is involved in regulation of secretory phospholipase A2-IIa expression in prostate cancer. Oncol Rep. 2011;25:1511–6.PubMed Dong Z, Liu Y, Levin L, Oleksowicz L, Wang J, Lu S. Vav3 oncogene is involved in regulation of secretory phospholipase A2-IIa expression in prostate cancer. Oncol Rep. 2011;25:1511–6.PubMed
18.
go back to reference Dong Z, Liu Y, Lu S, Wang A, Lee K, Wang LH, et al. Vav3 oncogene is overexpressed and regulates cell growth and androgen receptor activity in human prostate cancer. Mol Endocrinol. 2006;20:2315–25.PubMedCrossRef Dong Z, Liu Y, Lu S, Wang A, Lee K, Wang LH, et al. Vav3 oncogene is overexpressed and regulates cell growth and androgen receptor activity in human prostate cancer. Mol Endocrinol. 2006;20:2315–25.PubMedCrossRef
19.
go back to reference Sauzeau V, Sevilla MA, Rivas-Elena JV, de Alava E, Montero MJ, López-Novoa JM, et al. Vav3 proto-oncogene deficiency leads to sympathetic hyperactivity and cardiovascular dysfunction. Nat Med. 2006;12:841–5.PubMedCentralPubMedCrossRef Sauzeau V, Sevilla MA, Rivas-Elena JV, de Alava E, Montero MJ, López-Novoa JM, et al. Vav3 proto-oncogene deficiency leads to sympathetic hyperactivity and cardiovascular dysfunction. Nat Med. 2006;12:841–5.PubMedCentralPubMedCrossRef
20.
go back to reference Sauzeau V, Carvajal-González JM, Riolobos AS, Sevilla MA, Menacho-Márquez M, Román AC, et al. Transcriptional factor aryl hydrocarbon receptor (Ahr) controls cardiovascular and respiratory functions by regulating the expression of the Vav3 proto-oncogene. J Biol Chem. 2011;286:2896–909.PubMedCrossRef Sauzeau V, Carvajal-González JM, Riolobos AS, Sevilla MA, Menacho-Márquez M, Román AC, et al. Transcriptional factor aryl hydrocarbon receptor (Ahr) controls cardiovascular and respiratory functions by regulating the expression of the Vav3 proto-oncogene. J Biol Chem. 2011;286:2896–909.PubMedCrossRef
23.
go back to reference Wander SA, Zhao D, Slingerland JM. p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies. Clin Cancer Res. 2011;17:12–8.PubMedCentralPubMedCrossRef Wander SA, Zhao D, Slingerland JM. p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies. Clin Cancer Res. 2011;17:12–8.PubMedCentralPubMedCrossRef
24.
go back to reference Jeong JB, Lee SH. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells. Biochem Biophys Res Commun. 2013;430:381–6.PubMedCrossRef Jeong JB, Lee SH. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells. Biochem Biophys Res Commun. 2013;430:381–6.PubMedCrossRef
25.
go back to reference Li Z, Miao Z, Jin G, Li X, Li H, Lv Z, et al. βig-h3 supports gastric cancer cell adhesion, migration and proliferation in peritoneal carcinomatosis. Mol Med Report. 2012;6:558–64. Li Z, Miao Z, Jin G, Li X, Li H, Lv Z, et al. βig-h3 supports gastric cancer cell adhesion, migration and proliferation in peritoneal carcinomatosis. Mol Med Report. 2012;6:558–64.
26.
go back to reference Citterio C, Menacho-Márquez M, García-Escudero R, Larive RM, Barreiro O, Sánchez-Madrid F, et al. The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells. Sci Signal. 2012;5:ra71.PubMedCrossRef Citterio C, Menacho-Márquez M, García-Escudero R, Larive RM, Barreiro O, Sánchez-Madrid F, et al. The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells. Sci Signal. 2012;5:ra71.PubMedCrossRef
27.
go back to reference Kamoshida G, Matsuda A, Sekine W, Mizuno H, Oku T, Itoh S, et al. Monocyte differentiation induced by co-culture with tumor cells involves RGD-dependent cell adhesion to extracellular matrix. Cancer Lett. 2012;315:145–52.PubMedCrossRef Kamoshida G, Matsuda A, Sekine W, Mizuno H, Oku T, Itoh S, et al. Monocyte differentiation induced by co-culture with tumor cells involves RGD-dependent cell adhesion to extracellular matrix. Cancer Lett. 2012;315:145–52.PubMedCrossRef
28.
go back to reference Lukaszewicz-Zając M, Mroczko B, Szmitkowski M. Gastric cancer—the role of matrix metalloproteinases in tumor progression. Clin Chim Acta. 2011;412:1725–30.PubMedCrossRef Lukaszewicz-Zając M, Mroczko B, Szmitkowski M. Gastric cancer—the role of matrix metalloproteinases in tumor progression. Clin Chim Acta. 2011;412:1725–30.PubMedCrossRef
29.
go back to reference Osinsky S, Bubnovskaya L, Ganusevich I, Kovelskaya A, Gumenyuk L, Olijnichenko G, et al. Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival. Clin Transl Oncol. 2011;13:133–8.PubMedCrossRef Osinsky S, Bubnovskaya L, Ganusevich I, Kovelskaya A, Gumenyuk L, Olijnichenko G, et al. Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival. Clin Transl Oncol. 2011;13:133–8.PubMedCrossRef
Metadata
Title
Inhibition of gastric cancer cell growth and invasion through siRNA-mediated knockdown of guanine nucleotide exchange factor Vav3
Authors
Bibo Tan
Yong Li
Qun Zhao
Liqiao Fan
Dong Wang
Yü Liu
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1204-2

Other articles of this Issue 2/2014

Tumor Biology 2/2014 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