Sublocalization of Rab23, a mediator of Sonic hedgehog signaling pathway, in hepatocellular carcinoma cell lines

Mol Med Rep. 2012 Dec;6(6):1276-80. doi: 10.3892/mmr.2012.1094. Epub 2012 Sep 20.

Abstract

The novel member of the Rab family of GTPases, Rab23, is an essential negative regulator of the Sonic hedgehog (Shh) signaling pathway. Loss of function mutation of the Rab23 gene causes abnormal development of the neural tube in mice and in certain human congenital diseases. The aberrant overexpression of Rab23 has been associated with various diseases, such as gastric, hepatocellular and lung cancer. The exact function of Rab23 in hepatocellular carcinomas (HCCs), however, remains unknown. Previously, we reported the abnormal sublocalization of Rab23 in lung cancers. In the current study, we investigated the role of Rab23 in HCCs. We report the distinct sublocalization pattern of Rab23 in HCC cell lines. This difference depends on the GDP/GTP-binding form, and inhibition of the Rab23 cycle decreases the expression and nuclear localization of Gli1.

Keywords: Rab23; hepatocellular carcinoma; Sonic hedgehog pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Hedgehog Proteins / metabolism*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Microscopy, Confocal
  • Mutation
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger Protein GLI1
  • rab GTP-Binding Proteins / analysis*
  • rab GTP-Binding Proteins / antagonists & inhibitors
  • rab GTP-Binding Proteins / metabolism

Substances

  • GLI1 protein, human
  • Hedgehog Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • RAB23 protein, human
  • rab GTP-Binding Proteins