Full Text:   <3571>

CLC number: R734.2

On-line Access: 2013-06-04

Received: 2012-07-23

Revision Accepted: 2012-09-25

Crosschecked: 2013-05-22

Cited: 2

Clicked: 6860

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2013 Vol.14 No.6 P.460-467


Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells

Author(s):  Guo-dong Xu, Xin-bao Shi, Le-bo Sun, Qing-yun Zhou, Da-wei Zheng, Huo-shun Shi, Yong-liang Che, Zi-shan Wang, Guo-feng Shao

Affiliation(s):  Department of Thoracic & Cardiovascular Surgery, Lihuili Hospital, Ningbo Medical Center, Affiliated Hospital of Medical School, Ningbo University, Ningbo 315041, China; more

Corresponding email(s):   guofengshaolihuili@163.com

Key Words:  Non-small-cell lung cancer (NSCLC), Epithelial-mesenchymal transition (EMT), Eukaryotic initiation factor 5A-2 (eIF5A-2), Transforming growth factor (TGF)-β, 1, A549

Guo-dong Xu, Xin-bao Shi, Le-bo Sun, Qing-yun Zhou, Da-wei Zheng, Huo-shun Shi, Yong-liang Che, Zi-shan Wang, Guo-feng Shao. Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells[J]. Journal of Zhejiang University Science B, 2013, 14(6): 460-467.

@article{title="Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells",
author="Guo-dong Xu, Xin-bao Shi, Le-bo Sun, Qing-yun Zhou, Da-wei Zheng, Huo-shun Shi, Yong-liang Che, Zi-shan Wang, Guo-feng Shao",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells
%A Guo-dong Xu
%A Xin-bao Shi
%A Le-bo Sun
%A Qing-yun Zhou
%A Da-wei Zheng
%A Huo-shun Shi
%A Yong-liang Che
%A Zi-shan Wang
%A Guo-feng Shao
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 6
%P 460-467
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200200

T1 - Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells
A1 - Guo-dong Xu
A1 - Xin-bao Shi
A1 - Le-bo Sun
A1 - Qing-yun Zhou
A1 - Da-wei Zheng
A1 - Huo-shun Shi
A1 - Yong-liang Che
A1 - Zi-shan Wang
A1 - Guo-feng Shao
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 6
SP - 460
EP - 467
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200200

Background: epithelial-mesenchymal transition (EMT) is believed to be the critical process in malignant tumor invasion and metastases, and has a great influence on improving the survival rate in non-small-cell lung cancer (NSCLC) patients. Recent studies suggested that eukaryotic initiation factor 5A-2 (eIF5A-2) might serve as an adverse prognostic marker of survival. We detected eIF5A-2 in NSCLC a549 cells, and found that the invasive capability correlates with the eIF5A-2 expression. Methods: transforming growth factor (TGF)-β;1 was used to induce EMT in a549 cells. Western blotting, immunofluorescence, wound healing assay, and transwell-matrigel invasion chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of eIF5A-2. We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence. We tested the change of migration and invasion capabilities of a549 cells by the wound healing assay and transwell-matrigel invasion chambers. Results: After stimulating with TGF-β1, almost all a549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities. These cells also had higher eIF5A-2 protein expression. Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly. Conclusions: The expression of eIF5A-2 was up-regulated following EMT phenotype changes in a549 cells, which correlated with enhanced tumor invasion and metastatic capabilities. Furthermore, in the a549 cell line, the process of EMT phenotype change could be reversed by eIF5A-2 siRNA, with a consequent weakening of both invasive and metastatic capabilities.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Chen, W., Luo, J.H., Hua, W.F., Zhou, F.J., Lin, M.C., Kung, H.F., Xie, D., 2009. Overexpression of EIF-5A2 is an independent predictor of outcome in patients of urothelial carcinoma of the bladder treated with radical cystectomy. Cancer Epidemiol. Biomarkers Prev., 18(2):400-408.

[2]Clement, P.M., Hanauske-Abel, H.M., Wolff, E.C., Kleinman, H.K., Park, M.H., 2002. The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro. Int. J. Cancer, 100(4):491-498.

[3]Clement, P.M., Henderson, C.A., Jenkins, Z.A., Smit-McBride, Z., Wolff, E.C., Hershey, J.W., Johansson, H.E., 2003. Identification and characterization of eukaryotic initiation factor 5A-2. Eur. J. Biochem., 270(21):4254-4263.

[4]Clement, P.M., Johansson, H.E., Wolff, E.C., Park, M.H., 2006. Differential expression of eIF5A-1 and eIF5A-2 in human cancer cells. FEBS J., 273(6):1102-1114.

[5]Grünert, S., Jechlinger, M., Beug, H., 2003. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat. Rev. Mol. Cell Biol., 4(8):657-665.

[6]Guan, X.Y., Fung, J.M., Ma, N.F., Lau, S.H., Tai, L.S., Xie, D., Sham, J.S., 2004. Oncogenic role of eIF-5A2 in the development of ovarian cancer. Cancer Res., 64(12):4197-4200.

[7]He, L.R., Zhao, H.Y., Li, B.K., Liu, Y.H., Liu, M.Z., Guan, X.Y., Xie, D., 2011. Overexpression of eIF5A-2 is an adverse prognostic marker of survival in stage I non-small cell lung cancer patients. Int. J. Cancer, 129(1):143-150.

[8]Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., Thun, M.J., 2008. Cancer statistics, 2008. CA Cancer J. Clin., 58(2):71-96.

[9]Kasai, H., Allen, J.T., Mason, R.M., Kamimura, T., Zhang, Z., 2005. TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir. Res., 6(1):56.

[10]Kim, J.H., Jang, Y.S., Eom, K.S., Hwang, Y.I., Kang, H.R., Jang, S.H., Kim, D.G., 2007. Transforming growth factor β1 induces epithelial-to-mesenchymal transition of A549 cells. J. Korean Med. Sci., 22(5):898-904.

[11]Li, A.L., Li, H.Y., Jin, B.F., Ye, Q.N., Zhou, T., Yu, X.D., Zhang, X.M., 2004. A novel eIF5A complex functions as a regulator of p53 and p53-dependent apoptosis. J. Biol. Chem., 279(47):49251-49258.

[12]Maitah, M.Y., Ali, S., Ahmad, A., Gadgeel, S., Sarkar, F.H., 2011. Up-regulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells. PLoS One, 6(1):e16068.

[13]Nishimura, K., Murozumi, K., Shirahata, A., Park, M.H., Kashiwagi, K., Igarashi, K., 2005. Independent roles of eIF5A and polyamines in cell proliferation. Biochem. J., 385(Pt3):779-785.

[14]Nozawa, N., Hashimoto, S., Nakashima, Y., Matsuo, Y., Koga, T., Sugio, K., Sueishi, K., 2006. Immunohistochemical α- and β-catenin and E-cadherin expression and their clinicopathological significance in human lung adenocarcinoma. Pathol. Res. Pract., 202(9):639-650.

[15]Rosell, R., Felip, E., Taron, M., Majo, J., Mendez, P., Sanchez-Ronco, M., Maestre, J., 2004. Gene expression as a predictive marker of outcome in stage IIB-IIIA-IIIB non-small cell lung cancer after induction gemcitabine-based chemotherapy followed by resectional surgery. Clin. Cancer Res., 10(12):4215s-4219s.

[16]Saito, R.A., Watabe, T., Horiguchi, K., Kohyama, T., Saitoh, M., Nagase, T., Miyazono, K., 2009. Thyroid transcription factor-1 inhibits transforming growth factor-β-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. Cancer Res., 69(7):2783-2791.

[17]Tang, D.J., Dong, S.S., Ma, N.F., Xie, D., Chen, L., Fu, L., Guan, X.Y., 2010. Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma. Hepatology, 51(4):1255-1263.

[18]Thiery, J.P., 2002. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer, 2(6):442-454.

[19]Wozniak, A.J., Gadgeel, S.M., 2007. Adjuvant treatment of non-small-cell lung cancer: how do we improve the cure rates further? Oncology, 21(2):163-171.

[20]Xie, D., Ma, N.F., Pan, Z.Z., Wu, H.X., Liu, Y.D., Wu, G.Q., Guan, X.Y., 2008. Overexpression of EIF-5A2 is associated with metastasis of human colorectal carcinoma. Hum. Pathol., 39(1):80-86.

[21]Yang, G.F., Xie, D., Liu, J.H., Luo, J.H., Li, L.J., Hua, W.F., Guan, X.Y., 2009. Expression and amplification of eIF-5A2 in human epithelial ovarian tumors and overexpression of EIF-5A2 is a new independent predictor of outcome in patients with ovarian carcinoma. Gynecol. Oncol., 112(2):314-318.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE