The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression

Mol Neurobiol. 2016 Sep;53(7):4431-7. doi: 10.1007/s12035-015-9378-9. Epub 2015 Aug 6.

Abstract

Rab31, a member of the Ras superfamily, is reported to play a role in tumor development and progression. However, the detailed role of Rab31 in proliferation and apoptosis of cancer cells is still unclear. Here, we used different cell lines, such as glioblastoma, and cervical cancer, to investigate the role of Rab31 in cancer progression. We found that Rab31 promotes U87 and SiHa cell proliferation via activation of G1/S checkpoint transitions, accompanied with an increase of cyclin D1, cyclin A, and cyclin B1. Meanwhile, Rab31 inhibits U87 and SiHa cell apoptosis, and decreased the BAX and PIG3 expression, but enhanced BCL2 expression. In addition, Rab31 induces N-cadherin, Vimentin, and Snail expression, and inhibits E-cadherin expression to regulate proliferation and migration. Besides, we observed that ERK1/2 and PI3k/AKT pathways are required for Rab31-induced cell proliferation and migration. In vivo, the knockdown of Rab31 suppresses tumor mass growth. In conclusion, our data highlight the crucial role of Rab31 in cancer progression, proliferation, and apoptosis, and indicates that Rab31 may be a useful and effective target for the clinical therapy of most cancers.

Keywords: Apoptosis; Cancer; Proliferation; Rab31.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation
  • Cyclins / metabolism
  • Disease Progression*
  • Epithelial-Mesenchymal Transition
  • G1 Phase
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice, Nude
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • S Phase
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Cyclins
  • RAB31 protein, human
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • rab GTP-Binding Proteins