Girdin expression in cervical carcinoma and its role in the malignant properties of HeLa cells

Jiang,Ping; Ren,Ya‑Li; Li,Jia‑Liang; Luo,Jun

doi:10.3892/ol.2016.4250

Girdin expression in cervical carcinoma and its role in the malignant properties of HeLa cells

Authors:
- Ping Jiang
- Ya‑Li Ren
- Jia‑Liang Li
- Jun Luo
View Affiliations

Affiliations: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China, Laboratory of Electron Microscopy, Peking University First Hospital, Beijing 100034, P.R. China, Clinical Laboratory, Fuda Cancer Hospital, Guangzhou, Guangdong 510665, P.R. China
Published online on: February 18, 2016 https://doi.org/10.3892/ol.2016.4250
Pages: 2440-2444

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

Cervical cancer is a major cause of mortality in females worldwide, with the majority of cases reported in developing countries. The molecular mechanisms of this disease are unclear. However, increasing evidence indicates that the expression or overexpression of Girdin is associated with a poor prognosis in a variety of cancer types. Therefore, the aim of the current study was to evaluate the potential association between Girdin expression, and malignant properties of cervical cancer lesions and HeLa cells. Girdin protein expression was examined in 87 samples of cervical squamous cell lesions, including intraepithelial neoplasia (grades I and Ⅲ) and invasive carcinoma, using immunohistochemical (IHC) staining. A short‑hairpin RNA (shRNA) approach was employed to specifically suppress the expression of Girdin mRNA in HeLa cells in vitro, allowing the role of Girdin in a number of malignant properties to be evaluated. Girdin protein was observed in the cytoplasm of 79/87 (90.8%) cervical cancer lesion specimens. However, no positive Girdin signals were identified in healthy cervical squamous epithelium samples. Furthermore, a significant correlation between Girdin expression and lesion grade was identified (Spearman's correlation coefficient, 0.566; P<0.001). When Girdin was suppressed by Girdin shRNA, the rate of HeLa cell growth was significantly reduced in vitro (P<0.05). Additional analysis determined that Girdin was associated with serum‑deprived induced HeLa apoptosis. Thus, patients with high‑grade cervical cancer tumors exhibited a strong expression for Girdin, and Girdin appears to key in HeLa cell proliferation and serum‑deprived induced apoptosis, supporting the hypothesis that Girdin may be important in the process of cervical carcinogenesis.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
2	Pisani P, Bray F and Parkin DM: Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 97:72–81. 2002. View Article : Google Scholar : PubMed/NCBI
3	Richart RM: A modified terminology for cervical intraepithelial neoplasia. Obstet Gynecol. 75:131–133. 1990.PubMed/NCBI
4	Creasman WJ: Preinvasive disease of the cervix. Clinical Gynecologic Oncology. DiSaia PJ and Creasman WJ: (6th). (CV Mosby, St. Louis, MO). 1–34. 2002. View Article : Google Scholar
5	Basu P and Chowdhury D: Cervical cancer screening & HPV vaccination: a comprehensive approach to cervical cancer control. Indian J Med Res. 130:241–246. 2009.PubMed/NCBI
6	Saleem A, Tristram A, Fiander A and Hibbitts S: Prophylactic HPV vaccination: a major breakthrough in the fight against cervical cancer? Minerva Med. 100:503–523. 2009.PubMed/NCBI
7	Magnusson PK, Sparén P and Gyllensten UB: Genetic link to cervical tumours. Nature. 400:29–30. 1999. View Article : Google Scholar : PubMed/NCBI
8	zur Hausen H: Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2:342–350. 2002. View Article : Google Scholar : PubMed/NCBI
9	Georgieva S, Iordanov V and Sergieva S: Nature of cervical cancer and other HPV-associated cancers. J BUON. 14:391–398. 2009.PubMed/NCBI
10	Jiang P, Enomoto A, Jijiwa M, et al: An actin-binding protein Girdin regulates the motility of breast cancer cells. Cancer Res. 68:1310–1318. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ghosh P, Beas AO, Bornheimer SJ, et al: A Gαi-GIV molecular complex binds epidermal growth factor receptor and determines whether cells migrate or proliferate. Mol Biol Cell. 21:2338–2354. 2010. View Article : Google Scholar : PubMed/NCBI
12	Mao JZ, Jiang P, Cui SP, et al: Girdin locates in centrosome and midbody and plays an important role in cell division. Cancer Sci. 103:1780–1787. 2012. View Article : Google Scholar : PubMed/NCBI
13	Weng L, Enomoto A, Ishida-Takagishi M, Asai N and Takahashi M: Girding for migratory cues: roles of the Akt substrate Girdin in cancer progression and angiogenesis. Cancer Sci. 101:836–842. 2010. View Article : Google Scholar : PubMed/NCBI
14	Dunkel Y, Ong A, Notani D, Mittal Y, Lam M, Mi X and Ghosh P: STAT3 protein up-regulates Gα-interacting vesicle-associated protein (GIV)/Girdin expression, and GIV enhances STAT3 activation in a positive feedback loop during wound healing and tumor invasion/metastasis. J Biol Chem. 287:41667–41683. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ling Y, Jiang P, Cui SP, et al: Clinical implications for girdin protein expression in breast cancer. Cancer Invest. 29:405–410. 2011. View Article : Google Scholar : PubMed/NCBI
16	Garcia-Marcos M, Jung BH, Ear J, Cabrera B, Carethers JM and Ghosh P: Expression of GIV/girdin, a metastasis-related protein, predicts patient survival in colon cancer. FASEB J. 25:590–599. 2011. View Article : Google Scholar : PubMed/NCBI
17	Natsume A, Kato T, Kinjo S, et al: Girdin maintains the stemness of glioblastoma stem cells. Oncogene. 31:2715–2724. 2012. View Article : Google Scholar : PubMed/NCBI
18	Liu C, Zhang Y, Xu H, Zhang R, Li H, Lu P and Jin F: Girdin protein: a new potential distant metastasis predictor of breast cancer. Med Oncol. 29:1554–1560. 2012. View Article : Google Scholar : PubMed/NCBI
19	Benedet JL, Bender H, Jones H 3rd, Ngan HY and Pecorelli S: FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 70:209–262. 2000. View Article : Google Scholar : PubMed/NCBI
20	Kitamura T, Asai N, Enomoto A, Maeda K, Kato T, Ishida M, Jiang P, Watanabe T, Usukura J, Kondo T, et al: Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin. Nat Cell Biol. 10:329–337. 2008. View Article : Google Scholar : PubMed/NCBI
21	Anai M, Shojima N, Katagiri H, et al: A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis. J Biol Chem. 280:18525–18535. 2005. View Article : Google Scholar : PubMed/NCBI
22	Kim DJ, Chan KS, Sano S and Digiovanni J: Signal transducer and activator of transcription 3 (stat3) in epithelial carcinogenesis. Mol Carcinog. 46:725–731. 2007. View Article : Google Scholar : PubMed/NCBI
23	Takemoto S, Ushijima K, Kawano K, et al: Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma. Br J Cancer. 101:967–972. 2009. View Article : Google Scholar : PubMed/NCBI