Elevated expression of STIM1 is involved in lung tumorigenesis

Yadong Wang,Li Li,Teng Pan,Ding Zhang,Haiyan Yang,Jiangmin Li,Haiyu Wang

doi:10.18632/oncotarget.13359

Abstract

This study aimed to address the potential role of STIM1 (stromal interaction molecule 1) in lung tumorigenesis. Colony formation in soft agar assay and tumorigenicity in nude mice assay were conducted. Western blot, immunohistochemistry and quantitative real-time polymerase chain reaction were used to measure the STIM1 expression. The distribution of cell cycle was detected by flow cytometry assay. Our results showed that the expression of STIM1 mRNA was significantly higher in human lung tumors than that in adjacent non-neoplastic lung tissues. Significantly increased expression of STIM1 mRNA and protein was observed in 16HBE-benzo(a)pyrene (BaP) cells and in BaP-treated mice lung tissues compared with 16HBE-control cells and the control group, respectively. Silencing STIM1 inhibited the proliferation and colony formation of A549 cells in in vitro experiments, attenuated the growth of tumor xenografts of A549 cells in in vivo experiments and induced the arrest of cell cycle in the G1 phase. The markedly decreased expression of cyclin D1 protein was observed in A549-shRNA-STIM1 cells as compared to A549-shRNA-control cells. The markedly increased expression of p21 protein was observed in A549-shRNA-STIM1 cells as compared to A549-shRNA-control cells. The expression levels of β-catenin and TGIF proteins were lower in A549-shRNA-STIM1 cells than those in A549-shRNA-control cells. In conclusion, this study indicated that the elevated expression of STIM1 might be involved in lung tumorigenesis.

Highlights

An estimated 1.8 million new lung cancer cases occurred in 2012, accounting for approximately 13% of total cancer diagnoses
Our results demonstrated that STIM1 mRNA expression was higher in human lung tumors than that in adjacent non-neoplastic lung tissues (P = 0.001) (Figure 1)
Higher expression of STIM1 mRNA was observed in lung tumors compared with adjacent non-neoplastic lung tissues, suggesting that STIM1 overexpression may be involved in lung tumorigenesis

Summary

Introduction

An estimated 1.8 million new lung cancer cases occurred in 2012, accounting for approximately 13% of total cancer diagnoses. Lung cancer was the most commonly diagnosed cancer and the leading cause of cancer-related death in 2012. Lung cancer was the leading cause of cancer-related death in more developed countries and the second leading cause of cancer-related death in less developed countries [1]. Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes [9,10,11]. The molecular mechanisms involved in lung tumorigenesis remain incompletely understood

Objectives

Results

Conclusion