GPM6B Inhibit PCa Proliferation by Blocking Prostate Cancer Cell Serotonin Absorptive Capacity.

Siyuan He,Yinghui Ding,Xiang Li,Zhenlin Huang,Zhankui Jia,Bowen Liu,Haoyue Sheng,Jian Ma

doi:10.1155/2020/8810756

Abstract

Prostate cancer is currently one of the most common fatal tumor types in men. Although multiple treatments can alleviate some cases, advanced prostate cancer, especially CRPC, still has a very poor prognosis. Therefore, early detection and diagnosis of prostate cancer have a very important role in the prognosis of patients. Glycoprotein M6B (GPM6B) is a transmembrane protein that belongs to the proteolipid protein family. GPM6B has been proved and can be used as a biomarker for gynecological malignancies and breast carcinoma. However, there are no studies that explored the functions of GPM6B in PCa. We explored differentially expressed genes in prostate cancer by analyzing TCGA data and found GPM6B downregulated in PCa tissues compared to that in normal prostate tissues. The GPM6B expression in PCa patient's tumor tissues was significantly related to clinical stage, T classification, lymph node metastasis, and distant metastasis, but not significantly related to age and Gleason score. Also, patients with highGPM6B expression had a better prognosis. The overexpression of GPM6B in prostate cancer cells could inhibit cell proliferation. Serotonin treatment could enhance the proliferation of PCa cell lines; moreover, fluoxetine could reverse this result. In conclusion, we identified GPM6B as a tumor suppressor in PCa. In mechanism, it can regulate the uptaking of serotonin and inhibit the growth of prostate cancer. These results suggested the potential function of GPM6B as a diagnostic marker of PCa and provided clues for the development of new treatment targets for PCa.

Highlights

Prostate cancer (PCa), the second most common cancer in men, is associated with high morbidity and mortality [1]
Glycoprotein M6B (GPM6B) is a transmembrane protein that belongs to the proteolipid protein family
The GPM6B expression level was analyzed in 94 PCa patients and confirms its negative relationship with PCa clinic pathological

Summary

Introduction

Prostate cancer (PCa), the second most common cancer in men, is associated with high morbidity and mortality [1]. Traditional treatments are not very effective in treating castration-resistant metastasis [4, 5]. For this reason, exploring the molecular mechanisms that promote PCa progression could supply ideas for a valid therapeutic strategy. Glycoprotein M6B (GPM6B) is a transmembrane protein that belongs to the proteolipid protein family. GPM6A and DM20 belong to the proteolipid protein family [6]. Earlier studies have shown that proteolipid proteins might work as housekeeping proteins that participate in intracellular transport [7]. GPM6B plays a role in regulating osteoblast function and mineralization induction [13]. GPM6B can be used as a marker of tumor angiogenesis [16] In a study of the gynecological malignancies, namely, endometrial cancer, uterine cancer, and ovarian cancer, the expression level of Gpm6B

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