Options
Annexin A4 Enhances Cell Migration Ability through Triggering Endoplasmic Reticulum Stress Signaling
Date Issued
2010
Date
2010
Author(s)
Chou, Yi-Te
Abstract
The annexin family is ubiquitous proteins capable of binding to membrane with their C-terminal annexin repeats in a Ca2+-dependent manner. The variances of N-terminal of each annexin member contribute to their wide variety of functions including vesicle trafficking, signaling, cell division, growth regulation and apoptosis. Their differentially expressions in distinct tumors are considered as biomarkers and may imply the participation in tumorgenesis. Our previous study showed that annexin A4, a member of annexin family, was overexpressed in both gastric tumor tissues and host cancer cells infected by Helicobacter pylori (H. pylori). Meanwhile, the production of IL-8, an indicator of infection, decreased after annexin A4 knockdown. To investigate the role of annexin A4 in gastric cancer cells, proteomics and network analysis were performed. 36 differentially expressed proteins and a network analysis related to protein folding were identified using Ingenuity Pathway Analysis software. Furthermore, we found ER stress pathway which may increase cell migration ability was very important in annexin A4-overexpressed cells. Therefore, we used western blotting, wound healing assay, cell migration ability assay to elucidate the expression levels of proteins involved in the response to ER stress and migration ability in annexin A4-overexpressed gastric cancer cells. Here, we show that annexin A4 overexpression not only increases ER stress related protein expression and migration ability but also activates two transcription factors, Nuclear factor kappa B (NF-kB) and c-myc, and triggers Akt phosphorylation. These changes might lead to a substantial rise in the expression of the eukaryotic initiation factor 4E (eIF4E) gene, ultimately promoting the migratory ability of gastric cancer cells. The phenomenon was reversed by treating cells with ER stress signaling inhibitor, 8-(N,N-Diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8). Our results demonstrated a plausible mechanism to explain the phenomena that migratory ability increased in annexin A4-overexpressed gastric cancer cells. Eventually, these findings provide useful information in gastric cancer therapy.
Subjects
Proteomics
annexin A4
gastric cancer
ER stress
cell migration
SDGs
Type
thesis
File(s)
No Thumbnail Available
Name
ntu-98-R97b43005-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):2ff24ba8609c389a1227b6c4a15b1880