EphA2 silencing in nasopharyngeal carcinoma leads to decreased proliferation, invasion and increased sensitization to paclitaxel

Tan,Pingqing; Liu,Yong; Yu,Changyun; Su,Zhongwu; Li,Guo; Zhou,Xiaojuan; Huang,Donghai; Zhang,Xin; Qiu,Yuanzheng; Tian,Yongquan

doi:10.3892/ol.2012.746

EphA2 silencing in nasopharyngeal carcinoma leads to decreased proliferation, invasion and increased sensitization to paclitaxel

Authors:
- Pingqing Tan
- Yong Liu
- Changyun Yu
- Zhongwu Su
- Guo Li
- Xiaojuan Zhou
- Donghai Huang
- Xin Zhang
- Yuanzheng Qiu
- Yongquan Tian
View Affiliations

Affiliations: Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China , Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan 410008, P.R. China, Department of Otolaryngology, Changsha No.1 Hospital, Changsha, Hunan 410013, P.R. China
Published online on: June 8, 2012 https://doi.org/10.3892/ol.2012.746
Pages: 429-434

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

EphA2 is frequently overexpressed and functionally altered in a variety of human cancers. However, its roles in human nasopharyngeal carcinoma (NPC) remain unclear. To investigate the roles of EphA2 in the development and progression of NPC, we initially evaluated the expression pattern of EphA2 protein in NPC tissues using western blotting and CCK-8 assay. Fluorescence-activated cell sorting analysis and invasion assay were conducted to observe the effects of EphA2 inhibition in vivo. Our results demonstrated that EphA2 was overexpressed in NPC specimens and the expression of EphA2 was significantly associated with T classification, advanced clinical stage and lymph node metastasis. Moreover, human NPC 5-8F cells were infected with lentiviral vector-mediated EphA2-specific shRNA, which resulted in the significant inhibition of cell growth, invasion of 5-8F cells and markedly enhanced the sensitivity of 5-8F cells to the chemotherapeutic agent paclitaxel in vitro. Collectively, our results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human NPC.

View Figures

View References

1	Fahraeus R, Fu HL, Ernberg I, et al: Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 42:329–338. 1988. View Article : Google Scholar : PubMed/NCBI
2	Shanmugaratnam K: Nasopharyngeal carcinoma: epidemiology, histopathology and aetiology. Ann Acad Med Singapore. 9:289–295. 1980.PubMed/NCBI
3	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics. CA Cancer J Clin. 60:277–300. 2010.
4	Teo P, Shiu W, Leung SF and Lee WY: Prognostic factors in nasopharyngeal carcinoma investigated by computer tomography - an analysis of 659 patients. Radiother Oncol. 23:79–93. 1992. View Article : Google Scholar : PubMed/NCBI
5	Tan EH, Khoo KS, Wee J, et al: Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma. Ann Oncol. 10:235–237. 1999. View Article : Google Scholar : PubMed/NCBI
6	Pasquale EB: Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer. 10:165–180. 2010. View Article : Google Scholar : PubMed/NCBI
7	Pasquale EB: Eph-ephrin bidirectional signaling in physiology and disease. Cell. 133:38–52. 2008. View Article : Google Scholar : PubMed/NCBI
8	Sulman EP, Tang XX, Allen C, et al: ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers. Genomics. 40:371–374. 1997. View Article : Google Scholar : PubMed/NCBI
9	Brantley-Sieders DM, Zhuang G, Hicks D, et al: The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest. 118:64–78. 2008. View Article : Google Scholar
10	Lu C, Shahzad MM, Wang H, et al: EphA2 overexpression promotes ovarian cancer growth. Cancer Biol Ther. 7:1098–1103. 2008. View Article : Google Scholar : PubMed/NCBI
11	Zelinski DP, Zantek ND, Stewart JC, Irizarry AR and Kinch MS: EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res. 61:2301–2306. 2001.PubMed/NCBI
12	Zantek ND, Azimi M, Fedor-Chaiken M, Wang B, Brackenbury R and Kinch MS: E-cadherin regulates the function of the EphA2 receptor tyrosine kinase. Cell Growth Differ. 10:629–638. 1999.PubMed/NCBI
13	Lin YG, Han LY, Kamat AA, et al: EphA2 overexpression is associated with angiogenesis in ovarian cancer. Cancer. 109:332–340. 2007. View Article : Google Scholar : PubMed/NCBI
14	Han L, Dong Z, Qiao Y, et al: The clinical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas. Gynecol Oncol. 99:278–286. 2005. View Article : Google Scholar : PubMed/NCBI
15	Brannan JM, Dong W, Prudkin L, et al: Expression of the receptor tyrosine kinase EphA2 is increased in smokers and predicts poor survival in non-small cell lung cancer. Clin Cancer Res. 15:4423–4430. 2009. View Article : Google Scholar : PubMed/NCBI
16	Liu F, Park PJ, Lai W, et al: A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res. 66:10815–10823. 2006. View Article : Google Scholar : PubMed/NCBI
17	Taddei ML, Parri M, Angelucci A, et al: EphA2 induces metastatic growth regulating amoeboid motility and clonogenic potential in prostate carcinoma cells. Mol Cancer Res. 9:149–160. 2011. View Article : Google Scholar : PubMed/NCBI
18	Herrem CJ, Tatsumi T, Olson KS, et al: Expression of EphA2 is prognostic of disease-free interval and overall survival in surgically treated patients with renal cell carcinoma. Clin Cancer Res. 11:226–231. 2005.PubMed/NCBI
19	Liu Y, Xie C, Zhang X, et al: Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer. 46:3007–3015. 2010. View Article : Google Scholar : PubMed/NCBI
20	Liu Y, Zhang X, Qiu Y, et al: Clinical significance of EphA2 expression in squamous-cell carcinoma of the head and neck. J Cancer Res Clin Oncol. 137:761–769. 2011. View Article : Google Scholar : PubMed/NCBI
21	Johnson FM, Garden AS, Palmer JL, et al: A phase I/II study of neoadjuvant chemotherapy followed by radiation with boost chemotherapy for advanced T-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 63:717–724. 2005. View Article : Google Scholar : PubMed/NCBI
22	Liu Y, Yu C, Qiu Y, et al: Downregulation of EphA2 expression suppresses the growth and metastasis in squamous-cell carcinoma of the head and neck in vitro and in vivo. J Cancer Res Clin Oncol. 138:195–202. 2012. View Article : Google Scholar : PubMed/NCBI
23	Zhu G, Xiao D, Chen Q and Zhu Y: The expression and its potentially clinical significance of EphA2 in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 25:827–829. 8332011.(In Chinese).
24	Abraham S, Knapp DW, Cheng L, et al: Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder. Clin Cancer Res. 12:353–360. 2006. View Article : Google Scholar : PubMed/NCBI
25	Brannan JM, Sen B, Saigal B, et al: EphA2 in the early pathogenesis and progression of non-small cell lung cancer. Cancer Prev Res (Phila). 2:1039–1049. 2009. View Article : Google Scholar : PubMed/NCBI
26	Kinch MS, Moore MB and Harpole DH Jr: Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival. Clin Cancer Res. 9:613–618. 2003.PubMed/NCBI
27	King AD, Ahuja AT, Leung SF, et al: Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease. Head Neck. 22:275–281. 2000. View Article : Google Scholar : PubMed/NCBI
28	Leung SF, Teo PM, Shiu WW, Tsao SY and Leung TW: Clinical features and management of distant metastases of nasopharyngeal carcinoma. J Otolaryngol. 20:27–29. 1991.PubMed/NCBI
29	Ciuleanu TE, Fountzilas G, Ciuleanu E, Plataniotis M, Todor N and Ghilezan N: Paclitaxel and carboplatin in relapsed or metastatic nasopharyngeal carcinoma: a multicenter phase II study. J BUON. 9:161–165. 2004.PubMed/NCBI
30	Landen CN Jr, Chavez-Reyes A, Bucana C, et al: Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 65:6910–6918. 2005. View Article : Google Scholar : PubMed/NCBI