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Role of EHD2 in migration and invasion of human breast cancer cells

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Tumor Biology

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Abstract

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.

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Acknowledgments

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.

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Author notes

    Authors and Affiliations

    1. Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yishan Road, Shanghai, 200233, China

      Xiaojing Yang & Aina He

    2. Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China

      Hanru Ren

    3. Department of Immunology, Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China

      Li Yao

    4. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China

      Xueyu Chen

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    1. Xiaojing Yang
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    2. Hanru Ren
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    Corresponding author

    Correspondence to Xiaojing Yang.

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    Xiaojing Yang and Hanru Ren contributed equally to this work.

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    Yang, X., Ren, H., Yao, L. et al. Role of EHD2 in migration and invasion of human breast cancer cells. Tumor Biol. 36, 3717–3726 (2015). https://doi.org/10.1007/s13277-014-3011-9

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    • DOI: https://doi.org/10.1007/s13277-014-3011-9

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