Expression of tumor necrosis factor receptor-assicated factor 4 correlates with expression of Girdin and promotes nuclear translocation of Girdin in breast cancer

Wang,Ailian; Wang,Jian; Sun,Lili; Jin,Juan; Ren,Huayan; Yang,Fan; Diao,Kexin; Wei,Minjie; Mi,Xiaoyi

doi:10.3892/mmr.2015.3211

May-2015 Volume 11 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

May-2015 Volume 11 Issue 5

Full Size Image

Article

Expression of tumor necrosis factor receptor-assicated factor 4 correlates with expression of Girdin and promotes nuclear translocation of Girdin in breast cancer

Authors:
- Ailian Wang
- Jian Wang
- Lili Sun
- Juan Jin
- Huayan Ren
- Fan Yang
- Kexin Diao
- Minjie Wei
- Xiaoyi Mi
View Affiliations / Copyright

Affiliations: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Pathology, Shaanxi Baoji Centre Hospital, Baoji, Shaanxi 721008, P.R. China, Department of Pharmacology, Pharmaceutical College, China Medical University, Shenyang, Liaoning 110001, P.R. China
Pages: 3635-3641
|
Published online on: January 16, 2015

https://doi.org/10.3892/mmr.2015.3211
Expand metrics +

Abstract

Overexpression of tumor necrosis factor receptor‑associated factor 4 (TRAF4) has been reported in several human malignancies; however its association with Girdin in breast cancer is unclear. The aim of the present study was to analyze the correlation, expression and nuclear and cytoplasmic localizations of TRAF4 and Girdin in breast cancer tissues. Tissue samples from 38 patients with breast cancer, the MCF‑10A normal mammary epithelial cell line, the MCF‑7 estrogen‑receptor (ER)‑positive and MDA‑MB‑231 ER‑negative breast cancer cell lines were used in the present study. The results demonstrated that cytoplasmic expression of TRAF4 was positively correlated with cytoplasmic expression of Girdin. Furthermore, coexpression of TRAF4 and Girdin was highest in tissue samples from patients with lymph node metastases. Girdin was observed to be predominantly expressed in the cytoplasm of breast cancer cells; however TRAF4 promoted its translocation to the nucleus. These findings suggest that cytoplasmic expression of TRAF4 may be a novel potential marker for cell migration in breast cancer.

View Figures

View References

1	Xie P: TRAF molecules in cell signaling and in human diseases. J Mol Signal. 8:72013. View Article : Google Scholar : PubMed/NCBI
2	Zhang L, Zhou F, García de Vinuesa A, et al: TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Mol Cell. 51:559–572. 2013. View Article : Google Scholar : PubMed/NCBI
3	Wang X, Jin C, Tang Y, Tang LY and Zhang YE: Ubiquitination of tumor necrosis factor receptor associated factor 4 (TRAF4) by Smad ubiquitination regulatory factor 1 (Smurf1) regulates motility of breast epithelial and cancer cells. J Biol Chem. 288:21784–21792. 2013. View Article : Google Scholar : PubMed/NCBI
4	Li W, Peng C, Lee MH, et al: TRAF4 is a critical molecule for Akt activation in lung cancer. Cancer Res. 73:6938–6950. 2013. View Article : Google Scholar : PubMed/NCBI
5	Camilleri-Broët S, Cremer I, Marmey B, et al: TRAF4 overexpression is a common characteristic of human carcinomas. Oncogene. 26:142–147. 2007. View Article : Google Scholar
6	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 :
7	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
8	Ghosh P, Garcia-Marcos M and Farquhar MG: GIV/Girdin is a rheostat that fine-tunes growth factor signals during tumor progression. Cell Adh Migr. 5:237–248. 2011. View Article : Google Scholar : PubMed/NCBI
9	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
10	Jun BY, Kim SW, Jung CK, et al: Expression of girdin in human colorectal cancer and its association with tumor progression. Dis Colon Rectum. 56:51–57. 2013. View Article : Google Scholar
11	Ghosh P, Garcia-Marcos M, Bornheimer SJ and Farquhar MG: Activation of Galphai3 triggers cell migration via regulation of GIV. J Cell Biol. 182:381–393. 2008. View Article : Google Scholar : PubMed/NCBI
12	Liu C, Zhang Y, Xu H, et al: Girdin protein: a new potential distant metastasis predictor of breast cancer. Med Oncol. 29:1554–1560. 2012. View Article : Google Scholar
13	Enomoto A, Ping J and Takahashi M: Girdin, a novel actin-binding protein, and its family of proteins possess versatile functions in the Akt and Wnt signaling pathways. Ann NY Acad Sci. 1086:169–184. 2006. View Article : Google Scholar : PubMed/NCBI
14	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
15	Esparza EM and Arch RH: TRAF4 functions as an intermediate of GITR-induced NF-kappaB activation. Cell Mol Life Sci. 61:3087–3092. 2004. View Article : Google Scholar : PubMed/NCBI
16	Yang J, Liao X, Agarwal MK, Barnes L, Auron PE and Stark GR: Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev. 21:1396–1408. 2007. View Article : Google Scholar : PubMed/NCBI
17	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
18	Lautenschlaeger T, Perry J, Peereboom D, et al: In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines. Radiat Oncol. 8:2462013. View Article : Google Scholar : PubMed/NCBI
19	Enomoto A, Murakami H, Asai N, et al: Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell. 9:389–402. 2005. View Article : Google Scholar : PubMed/NCBI
20	Yang WL, Wu CY, Wu J and Lin HK: Regulation of Akt signaling activation by ubiquitination. Cell Cycle. 9:487–497. 2010. View Article : Google Scholar : PubMed/NCBI
21	Lin K: The Akt DUBbed InAktive. Sci Signal. 6:pe12013.PubMed/NCBI