Role of EHD2 in migration and invasion of human breast cancer cells
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Eps15 homology domain-containing 2 (EHD2) is a tumor suppressor gene, overexpressed in several solid tumors, including ovarian cancer and esophageal squamous cell carcinoma. The current study examined the expression and the role of EHD2 in human breast cancer. EHD2 expression was determined by Western blot and immunohistochemistry (IHC) in 80 breast cancer and paired noncancerous breast tissues. Correlations between clinicopathologic variables, overall survival, and EHD2 expression were analyzed. We investigated the role of EHD2 in breast cancer migration and invasion by wound healing assay and trans-well invasion assays. A notably lower level of EHD2 expression was found in breast cancer tissues. EHD2 expression was associated with histological grade, lymph node metastasis, and tumor size. Expression of EHD2 was found to be an independent prognostic factor in breast cancer patients. Furthermore, overexpression of EHD2 suppressed, while elimination of EHD2 promoted, the migration and invasion of breast cancer cells. Molecular data showed that EHD2 inhibited breast cancer migration and invasion probably by dampening the expression of Ras-related C3 botulinum toxin substrate 1 (Rac1). Downregulation of EHD2 was associated with migration and invasion by abrogating the expression of Rac1 in breast cancer patients. EHD2 may serve as a prognostic marker in breast cancer.
KeywordsEHD2 Rac1 Migration Invasion Breast cancer
We thank Depeng Zhao, from the Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, for his helpful discussion and careful revision of the English manuscript.
Conflicts of interest
- 10.Bignotti E, Tassi RA, Calza S, Ravaggi A, Romani C, Rossi E, et al. Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: identification of novel molecular biomarkers for early diagnosis and therapy. Gynecol Oncol. 2006;103(2):405–16.CrossRefPubMedGoogle Scholar
- 15.Lin CW, Sun MS, Liao MY, Chung CH, Chi YH, Chiou LT et al. Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/cortactin signaling in breast cancer cells. Carcinogenesis. 2014;35(11):2425–5.Google Scholar
- 16.Elsayed HE, Akl MR, Ebrahim HY, Sallam AA, Haggag EG, Kamal AM et al. Discovery, optimization, and pharmacophore modeling of oleanolic acid and analogues as breast cancer cell migration and invasion inhibitors through targeting Brk/Paxillin/Rac1 axis. Chem Biol Drug Des. 2014. doi: 10.1111/cbdd.12380.
- 33.Huasong G, Zongmei D, Jianfeng H, Xiaojun Q, Jun G, Sun G et al. Serine protease inhibitor (SERPIN) B1 suppresses cell migration and invasion in glioma cells. Brain Res. 2014. doi: 10.1016/j.brainres.2014.06.017.