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Rab17 inhibits the tumourigenic properties of hepatocellular carcinomas via the Erk pathway

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Tumor Biology

Abstract

The small GTPase Rab17 is a member of the Rab family and plays a critical role in the regulation of membrane trafficking polarized eukaryotic cells. However, the role of Rab17 in hepatocellular carcinoma (HCC) is not clear. In the present study, we investigated the role of Rab17 in HCC tumourgenesis. The expressions of Rab17 in non-tumour hepatic tissues and HCCs were detected via immunohistochemistry. Rab17 was found in 31 of 48 (64.6 %) and in 23 of 62 (37.1 %) of non-tumour hepatic tissue samples and HCCs (P = 0.0068), respectively, and there were significant correlations between Rab17 reductions and unfavourable variables including tumour size (P = 0.0171), differentiation level (P = 0.0126), and lymph nodal (P = 0.0044) and distant metastases (P = 0.0047). To elucidate the role of Rab17 in HCC, we generated two Rab17-overexpressing HCC cell lines. Rab17 overexpression significantly inhibited the tumourigenic properties of HCC cells in vitro and in vivo as demonstrated by reduced cell proliferation and migration, elevated G1 arrest, and decreased tumour xenograft growth. However, the attenuated tumourigenic properties of the HCC cells that were induced by Rab17 overexpression were significantly rescued by the activator of the Erk pathway EGF, which indicates that the Erk pathway plays a critical role in the Rab17 up-regulation-induced reduced tumourigenic properties of HCC cells. Rab17 might act as a tumour suppressor gene in HCCs, and the anti-tumour effects of Rab17 might be partially mediated by the Erk pathway.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (81270880) and the Chinese Ministry of Science and Technology (2009CB521902).

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    Authors and Affiliations

    1. Department of Pathology, No. 401 Hospital of PLA, Qingdao, Shandong, 266071, China

      Kejia Wang & Li Wei

    2. Department of Physiology and Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China

      Li Liu, Ronghua Zhang & Wenjun Yuan

    3. Department of Traditional Chinese Medicine Resources, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China

      Zhujun Mao & Yaokang Xiong

    4. Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, 200032, China

      Qing Liang

    5. Department of Physiology, Second Military Medical University, Shanghai, 200433, China

      Wenjun Yuan

    6. Department of Vasculocardiology, No. 401 Hospital of PLA, 22 Minjiang Road, Qingdao, Shandong, 266071, China

      Li Wei

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    1. Kejia Wang
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    Correspondence to Wenjun Yuan or Li Wei.

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    Kejia Wang and Zhujun Mao contributed equally to this work.

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    Wang, K., Mao, Z., Liu, L. et al. Rab17 inhibits the tumourigenic properties of hepatocellular carcinomas via the Erk pathway. Tumor Biol. 36, 5815–5824 (2015). https://doi.org/10.1007/s13277-015-3251-3

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