Glycoprotein nonmetastatic melanoma protein B accelerates tumorigenesis of cervical cancer in vitro by regulating the Wnt/β-catenin pathway.

Shuxiang Xu,Xu Chen,Yan Liu,Dongping Li,Yingying Fan

doi:10.1590/1414-431x20187567

Abstract

Cervical cancer is one of the most common cancers among women around the world. However, the underlying mechanism involved in cervical cancer progression is incompletely known. In the present study, we determined the role of glycoprotein nonmetastatic melanoma protein B (GPNMB) in tumorigenesis of cervical cancer. According to the GEO database, we found that GPNMB expression was significantly higher in cervical cancer than in normal cervix epithelium. A similar pattern was observed in GPNMB expression in cultured cervical cancer cells and normal cervical epithelial cells. Compared with the control, GPNMB knockdown significantly decreased the proliferation and migration capacity, but enhanced the apoptosis capacity of SiHa and HeLa cells. Additionally, the activity of MMP-2 and MMP-9 were aberrantly increased in SiHa and HeLa cells compared with normal cervical epithelial cells, whereas their activities were strongly inhibited by GPNMB siRNA. Furthermore, Wnt/β-catenin signaling was activated by GPNMB in SiHa and HeLa cells. Increased MMP-2/MMP-9 expression was suppressed by Dkk-1, inhibitor of Wnt/β-catenin signaling, while it was enhanced by stimulator BIO. The proliferation, migration, and apoptosis capacity of HeLa cells were found to be affected by Dkk-1 and BIO to different extents. In conclusion, we demonstrated that GPNMB contributed to the tumorigenesis of cervical cancer, at least in part, by regulating MMP-2/MMP-9 activity in tumor cells via activation of canonical Wnt/β-catenin signaling. This might be a potential therapeutic target for treating human cervical cancer.

Highlights

Cervical cancer is one of the most common malignant cancers among women around the world
glycoprotein nonmetastatic melanoma protein B (GPNMB) was aberrantly expressed in human cervical cancer tissues and cells Based on the GEO database, GPNMB expression was significantly up-regulated in cervical cancer compared with normal cervix epithelium (Figure 1A)
These results suggested that dysregulation of GPNMB expression might be associated with the tumorigenesis of human cervical cancer

Summary

Introduction

Cervical cancer is one of the most common malignant cancers among women around the world. There are three principal histologic types of cervical cancer: adenocarcinoma, squamous carcinoma, and adeno-squamous carcinoma. Squamous carcinoma is the most common in patients with cervical cancer, including grade I (highly differentiated), grade II (moderately differentiated), and grade III (lowly differentiated). Infection by human papillomaviruses has been identified as the single most high-risk factor associated with human cervical cancer [2,3]. The papillomaviruses infection alone is unlikely to cause invasive cervical carcinoma. Increasing evidence suggests that there are many unidentified genetic alterations involved in the tumorigenesis of cervical cancer [4]. Further understanding is necessary to improve therapeutic strategies in human cervical cancer

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