Revealing the molecular mechanism of gastric cancer marker annexin A4 in cancer cell proliferation using exon arrays
Journal
PLoS ONE
Journal Volume
7
Journal Issue
9
Pages
e44615
Date Issued
2012
Author(s)
Abstract
Gastric cancer is a malignant disease that arises from the gastric epithelium. A potential biomarker for gastric cancer is the protein annexin A4 (ANXA4), an intracellular Ca2+ sensor. ANXA4 is primarily found in epithelial cells, and is known to be involved in various biological processes, including apoptosis, cell cycling and anticoagulation. In respect to cancer, ANXA4-overexpression has been observed in cancers of various origins, including gastric tumors associated with Helicobacter pylori infection. H. pylori induces ANXA4 expression and intracellular [Ca2+]i elevation, and is an important risk factor for carcinogenesis that results in gastric cancer. Despite this correlation, the role of ANXA4 in the progression of gastric tumors remains unclear. In this study, we have investigated whether ANXA4 can mediate the rate of cell growth and whether ANXA4 downstream signals are involved in tumorigenesis. After observing the rate of cell growth in real-time, we determined that ANXA4 promotes cell proliferation. The transcription gene profile of ANXA4-overexpressing cells was measured and analyzed by human exon arrays. From this transcriptional gene data, we show that overexpression of ANXA4 regulates genes that are known to be related to cancer, for example the activation of hyaluronan mediated motility receptor (RHAMM), AKT, and cyclin-dependent kinase 1 (CDK1) as well as the suppression of p21. The regulation of these genes further induces cancer cell proliferation. We also found Ca2+ could regulate the transmission of downstream signals by ANXA4. We suggest that ANXA4 triggers a signaling cascade, leading to increased epithelial cell proliferation, ultimately promoting carcinogenesis. These results might therefore provide a new insight for gastric cancer therapy, specifically through the modification of ANXA4 activity. ? 2012 Lin et al.
SDGs
Other Subjects
calcium ion; cyclin dependent kinase 1; hyaluronic acid; lipocortin 4; protein kinase B; protein p21; article; calcium signaling; cancer cell; carcinogenesis; cell growth; cell proliferation; controlled study; disease marker; exon; gene activity; gene expression regulation; gene overexpression; gene repression; growth rate; human; human cell; nonhuman; stomach cancer; transcription regulation; Annexin A4; Calcium; Cell Proliferation; Enzyme Activation; Exons; Helicobacter pylori; Humans; Signal Transduction; Stomach Neoplasms; Tumor Markers, Biological; Helicobacter pylori
Type
journal article