Zhu Dengyan, Liu Donglei, Wu Kai, Cheng Xingdong, Yang Yang
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Mol Carcinog. 2025 Jun;64(6):1057-1065. doi: 10.1002/mc.23909. Epub 2025 Mar 26.
The role and underlying mechanisms of G protein-coupled receptor 87 (GPR87) in esophageal squamous cell carcinoma (ESCC) remain unclear, despite its established oncogenic functions in other malignancies. This study examined the expression of GPR87 and its association with survival rate in ESCC using online databases. The expression of GPR87 in ESCC tissues was identified using immunohistochemistry, and a correlation analysis was carried out using ki-67 data. ESCC cells were transfected with GPR87 knockdown or overexpression plasmids, followed by functional assays such as, CCK-8 for cell viability, colony formation for proliferation, wound healing for migration, Transwell for invasion, and tube formation for angiogenesis. Western blot analysis was used to assess STAT3 phosphorylation and VEGFA expression. Additionally, a xenograft tumor model was established to investigate the effect of GPR87 on tumor growth in vivo. The findings demonstrated that GPR87 was highly expressed in ESCC tissues and its overexpression was associated with a poor patient survival. Transfection with a GPR87 overexpression plasmid increases the cell viability, invasion, proliferation, and angiogenesis of ESCC cells, while transfection with sh-GPR87 reversed these effects. Additionally, GPR87 controlled VEGFA expression levels by promoting STAT3 phosphorylation. Rescue trials further verified that GPR87 promotes the growth of ESCC by modulating STAT3. Moreover, in vivo studies validated that GPR87 knockdown suppressed tumor growth. In conclusion, the findings highlight GPR87 as a key regulator of VEGFA expression via STAT3 activation, contributing to ESCC malignancy. Targeting GPR87 may provide a potential therapeutic strategy for ESCC.
尽管G蛋白偶联受体87（GPR87）在其他恶性肿瘤中已被证实具有致癌功能，但其在食管鳞状细胞癌（ESCC）中的作用及潜在机制仍不清楚。本研究利用在线数据库检测了GPR87在ESCC中的表达及其与生存率的关系。采用免疫组织化学法鉴定ESCC组织中GPR87的表达，并利用ki-67数据进行相关性分析。用GPR87敲低或过表达质粒转染ESCC细胞，然后进行功能试验，如用CCK-8检测细胞活力、用集落形成试验检测增殖、用伤口愈合试验检测迁移、用Transwell试验检测侵袭、用管腔形成试验检测血管生成。采用蛋白质免疫印迹分析评估STAT3磷酸化和VEGFA表达。此外，建立了异种移植肿瘤模型，以研究GPR87对体内肿瘤生长的影响。研究结果表明，GPR87在ESCC组织中高表达，其过表达与患者生存率低相关。转染GPR87过表达质粒可增加ESCC细胞的活力、侵袭、增殖和血管生成，而转染sh-GPR87可逆转这些作用。此外，GPR87通过促进STAT3磷酸化来控制VEGFA表达水平。挽救试验进一步证实，GPR87通过调节STAT3促进ESCC的生长。此外，体内研究证实敲低GPR87可抑制肿瘤生长。总之，研究结果突出了GPR87作为通过激活STAT3调控VEGFA表达的关键调节因子，促进了ESCC的恶性发展。靶向GPR87可能为ESCC提供一种潜在的治疗策略。
