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RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway

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Tumor Biology

Abstract

Emerging evidence indicates that RhoE as novel member of the Rho GTPases family plays an essential role in carcinogenesis and tumor progression of human various tumors, but the functional significance of RhoE in human esophageal squamous cell carcinoma (ESCC) is still unclear. In the current study, RhoE expression in ESCC tissues and cells was examined, and the biological functions of RhoE in ESCC cells were determined. The results revealed that RhoE expression at mRNA and protein levels was significantly downregulated in ESCC tissues and cell lines (P < 0.05). RhoE expression was tightly associated with differentiation degree, clinical staging, and lymph node metastasis of the patients with ESCC (P < 0.05), but no significant correlations were found between RhoE expression and gender or age of the patients with ESCC (P > 0.05). Additionally, we found that downregulation of RhoE expression in ESCC cells promoted cell proliferation, cell cycle progression, as well as cell invasion in vitro, and inhibited cell apoptosis. Conversely, upregulation of RhoE expression in ESCC cells inhibited cell proliferation, arrested cell cycle at G0/G1 phase, reduced cell invasion, and promoted cell apoptosis. Furthermore, the downregulation of RhoE expression significantly reduced PTEN level and enhanced pAkt level; however, elevation of RhoE expression markedly increased PTEN level and decreased pAkt level. Stepwise investigations demonstrated that overexpression of RhoE in ESCC cells increased the expressions of p27 and bax proteins but decreased the expressions of cyclin D1 and bcl-2 proteins. These data demonstrate that RhoE may play a driving role in the development and progression of ESCC, and targeting the RhoE may be an effective and feasible approach for treatment of ESCC.

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (81071723), Natural Science Foundation of He’nan Educational Committee (2010A310008), and Key Technologies R & D Program of He’nan Province (112102310699).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, People’s Republic China

    Hui Zhao

  2. Department of Pathology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China

    Jianping Yang & Shenglei Li

  3. Department of Pharmacology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China

    Tianli Fan

  4. Department of General Surgery, Huaihe Hospital of Henan University, No.8 Baogong Lake North Road, Kaifeng, Henan, 475000, People’s Republic of China

    Xuequn Ren

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  1. Hui Zhao
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  4. Shenglei Li
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Correspondence to Shenglei Li or Xuequn Ren.

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Hui Zhao, Jianping Yang, and Tianli Fan contributed equally to this study.

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Zhao, H., Yang, J., Fan, T. et al. RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway. Tumor Biol. 33, 1363–1374 (2012). https://doi.org/10.1007/s13277-012-0384-5

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  • DOI: https://doi.org/10.1007/s13277-012-0384-5

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