P-010 - Snail mediates Rab25-induced gastric cancer cell EMT and invasiveness

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Gastric Cancer
Translational Research
Presenter H.Y. Lee
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors H.Y. Lee1, S.H. Kim2, B.Y. Jeong1, K.H. Cho1, C.G. Park1, J.H. Hong3
  • 1Konyang University, Daejeon/KR
  • 2Konyang University, Daejeon/
  • 3Chungnam National University College of Medicine & Hospital, Daejeon/KR

Abstract

Introduction

Rab25 is a member of the Rab11 subfamily and exclusively expressed in epithelial cells. As a small GTP-binding protein, Rab25 has been known to mediate recycling of proteins from the endosome to the plasma membrane. Cancer metastasis is multi-step events including epithelial-to-mesenchymal transition (EMT). Various transcription factors mediate EMT through downregulation of E-cadherin. In the present study, we investigate whether Rab25 induces EMT transcription factors, thereby increasing stomach cancer invasiveness.

Methods

Immunoblotting, quantitative RT-PCR and immunofluorescence assay were used to examine the expression of Rab25 and EMT factors. siRNAs of Rab25, Slug and Snail were transfected to determine their role in Rab25-induced stomach cancer cell EMT and invasiveness. Transwell invasion assay were used to determine cancer cell invasiveness.

Results

Ectopic expression of Rab25 marked reduced E-cadherin expression, while Snail expression was upregulated. In addition, Rab25 significantly aggravated cancer cell invasiveness. However, silencing Snail expression by utilizing specific siRNA significantly attenuated cancer cell invasion. In addition, Rab35 induced phosphorylation of Akt and GSK-3beta. However, pharmacological inhibition of Akt and GSK-3beta marked attenuated Rab25-induced Snail expression. Further, we observed that an integrin beta1 located upstream of an Akt/GSK-3beta signaling is important for Rab25-induced Snail expression and stomach cancer cell invasion.

Conclusion

Our results show for the first time that Snail mediates Rab25-induced stomach cancer cell EMT and invasiveness through an integrin beta1/Akt/GSK-3beta signaling cascade, providing novel biomarkers, and potential therapeutic targets for gastric cancer.