Tumor Biology

, Volume 36, Issue 8, pp 5815–5824 | Cite as

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

Research Article

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.

Keywords

Rab17 Small GTPases Hepatocellular carcinoma cells Signalling pathway 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Kejia Wang
    • 1
  • Zhujun Mao
    • 3
  • Li Liu
    • 2
  • Ronghua Zhang
    • 2
  • Qing Liang
    • 4
  • Yaokang Xiong
    • 3
  • Wenjun Yuan
    • 2
    • 5
  • Li Wei
    • 1
    • 6
  1. 1.Department of PathologyNo. 401 Hospital of PLAQingdaoChina
  2. 2.Department of Physiology and Key Laboratory of Fertility Preservation and Maintenance of Ministry of EducationNingxia Medical UniversityYinchuanChina
  3. 3.Department of Traditional Chinese Medicine Resources, College of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhouChina
  4. 4.Department of Physiology and PathophysiologyFudan University Shanghai Medical CollegeShanghaiChina
  5. 5.Department of PhysiologySecond Military Medical UniversityShanghaiChina
  6. 6.Department of VasculocardiologyNo. 401 Hospital of PLAQingdaoChina

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