KIAA1199 promotes migration and invasion by Wnt/β-catenin pathway and MMPs mediated EMT progression and serves as a poor prognosis marker in gastric cancer.

Shuqin Jia,Wenmei Li,Xiaohong Wang,Ziyu Li,Ke Ji,Mengmeng Feng,Jiafu Ji,Wenguo Jiang,Yi Feng,Yang Yang,Xuemin Feng,Ruiting Ma,Tingting Qu,Ying Hu,Aamir Ahmad

doi:10.1371/journal.pone.0175058

Abstract

BackgroundKIAA1199 was upregulated in diverse cancers, but the association of KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells and the related molecular mechanisms remain to be elucidated.MethodsKIAA1199 expression was analysed by reverse transcription-polymerase chain reaction assay (RT-PCR) and immunohistochemistry (IHC) in GC patient tissue. The small hairpin RNA (shRNA) was applied for the knockdown of endogenous KIAA1199 in NCI-N87 and AGS cells. MTT, colony formation, scratch wounding migration, transwell chamber migration and invasion assays were employed respectively to investigate the role of KIAA1199 in GC cells. The potential signaling pathway of KIAA1199 induced migration and invasion was detected.ResultsKIAA1199 was upregulated in GC tissue and was an essential independent marker for poor prognosis. Knockdown KIAA1199 suppressed the proliferation, migration and invasion in GC cells. KIAA1199 stimulated the Wnt/β-catenin signaling pathway and the enzymatic activity of matrix metalloproteinase (MMP) family members and thus accelerated the epithelial-to-mesenchymal transition (EMT) progression in GC cells.ConclusionThese findings demonstrated that KIAA1199 was upregulated in GC tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as an oncogene by promoting migration and invasion through the enhancement of Wnt/β-catenin signaling pathway and MMPs mediated EMT progression in GC cells.

Highlights

Gastric cancer (GC) is one of the most lethal malignancies and the third leading cause of cancer-related mortality [1]
These findings demonstrated that KIAA1199 was upregulated in gastric cancer (GC) tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as an oncogene by promoting migration and invasion through the enhancement of Wnt/β-catenin signaling pathway and matrix metalloproteinase (MMP) mediated epithelial-to-mesenchymal transition (EMT) progression in GC cells
The IHC analysis on the biopsies from123 GC patients showed that KIAA1199 protein expression had no significant effect on such clinical parameters regarding age, sex, vascular invasion and differentiation, but was correlated with depth of invasion, lymph node status (N-staging), metastasis and Tumor node metastasis (TNM) staging (T-staging: P

Summary

Introduction

Gastric cancer (GC) is one of the most lethal malignancies and the third leading cause of cancer-related mortality [1]. The expression of KIAA1199 was demonstrated to be especially upregulated in invasive breast cancer specimens and cell lines by large scale microarray and studies of breast cancer cell lines, which indicated that KIAA1199 was associated with cell proliferation, motility and apoptosis [5,8]. Proteomics analysis by two-dimensional gel electrophoresis and mass spectrometry assay revealed KIAA1199 was one novel protein that expressed abnormally in oral cancer, which was demonstrated by Realtime-PCR assay [6]. KIAA1199 was upregulated in diverse cancers, but the association of KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells and the related molecular mechanisms remain to be elucidated

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Results

Discussion

Conclusion