研究动态
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GOLM1通过激活前列腺癌TGFβ1 / Smad2信号传导促进上皮间充质转化。

GOLM1 Promotes Epithelial-Mesenchymal Transition by Activating TGFβ1/Smad2 Signaling in Prostate Cancer.

发表日期:2023
作者: Xuke Qin, Lin Liu, Yanze Li, Hongbo Luo, Hui Chen, Xiaodong Weng
来源: Cell Death & Disease

摘要:

背景:前列腺癌(PC)是全球男性中最常见的癌症之一。上皮-间充质转化(EMT)被认为在发展为可转移的去势抵抗性前列腺癌中发挥着关键作用,这种癌症导致了大多数的死亡病例。Golgi膜蛋白1(GOLM1)在前列腺癌中高表达,并已被鉴定为各种癌症EMT的驱动因子。然而,其在前列腺癌中的生物学功能和潜在机制仍然不清楚。 方法:利用Western blot和免疫组化分析检测前列腺癌中GOLM1的表达水平。我们过表达和沉默了不同前列腺癌细胞株中的GOLM1来研究GOLM1在癌细胞中的功能。Transwell测定和划痕愈合实验用于确定GOLM1在细胞EMT中如迁移和侵袭的作用。通过Western blot和Transwell测定检测GOLM1下游的TGF-β1/Smad2信号通路。 结果:GOLM1表达在前列腺癌中上调,与恶化预后相关。 GOLM1促进了前列腺癌细胞株(DU145和LNCaP)的迁移和侵袭能力。此外,TGF-β1/Smad2信号被GOLM1正调控以促进前列腺癌的EMT,然而此作用可以通过GOLM1沉默后的TGF-β1恢复或被p-Smad抑制剂SB431542所消除。 结论:GOLM1在前列腺癌中明显上调,并通过激活TGF-β1/Smad2信号通路促进前列腺癌细胞EMT过程,是一个极其重要的癌基因。因此,GOLM1有潜力成为前列腺癌诊断和预测患者预后的生物标志物。寻找针对GOLM1的有效和特异性抑制剂对前列腺癌治疗具有重要意义。
Background: Prostate cancer (PC) is one of the most commonly diagnosed cancer in men worldwide. Epithelial-mesenchymal transition (EMT) is considered to play a crucial role in the development of the metastatic castration-resistant prostate cancer, which causes the majority of the death cases in PC. Golgi membrane protein 1 (GOLM1) is highly expressed in PC and has been identified as a driver factor for EMT in various cancers. However, its biological functions and underlying mechanisms remain ambiguous in PC. Method: GOLM1 expression level of PC was detected by Western blot and immunohistochemistry analyses. To investigate GOLM1 functions in cancer cells, we overexpressed and knocked down GOLM1 in different prostate cancer cell lines. Transwell assay and wound healing assay were used to determine the role of GOLM1 in cell EMT, such as migration and invasion abilities. TGF-β1/Smad2 signaling pathway downstream of GOLM1 was detected by Western blot and Transwell assay. Result: GOLM1 expression is up-regulated in PC and correlated with a worse prognosis. GOLM1 promotes the abilities of migration and invasion in PC cell lines (DU145 and LNCaP). Furthermore, TGF-β1/Smad2 signaling is positively regulated by GOLM1 to facilitate EMT in PC, whereas this role can be restored by TGF-β1 after GOLM1 knockdown or be abrogated by p-Smad inhibitor SB431542. Conclusion: GOLM1 is significantly upregulated in PC and acts as a critical oncogene by promoting PC cell EMT process by activating TGF-β1/Smad2 signaling pathway. Therefore, GOLM1 has the potential to be a biomarker for PC diagnosis and to predict the prognosis of PC patients. It is of great significance to seek effective and specific inhibitor of GOLM1 for PC treatment as well.