TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway.
TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway.
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DOI：
10.3892/or.2018.6859
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发表时间：
2019-03
期刊：
影响因子：
4.2
通讯作者：
Cui H
中科院分区：
文献类型：
--
作者：
Hou J;Lv A;Deng Q;Zhang G;Hu X;Cui H
滋养层细胞表面抗原2（TROP 2）是一种单跨膜结构域蛋白，经常发现在各种类型的人类癌症中高度表达。然而，TROP 2在胶质母细胞瘤中的生物学功能和分子机制尚未完全阐明，特别是关于胶质母细胞瘤细胞的细胞增殖和转移。在本研究中，通过免疫组织化学分析和蛋白质印迹分析，证明了在胶质母细胞瘤组织和胶质母细胞瘤细胞系中TROP 2表达增加。TROP 2的高表达与胶质母细胞瘤患者的不良生存率显著相关。通过MTT法、BrdU掺入法、流式细胞仪和Transwell法检测TROP 2基因的表达，证明TROP 2基因的敲除抑制胶质母细胞瘤细胞的增殖和转移。我们发现，TROP 2基因敲低对胶质母细胞瘤细胞的影响与JAK 2和STAT 3磷酸化的抑制以及STAT 3靶基因转录的降低有关。此外，通过WP1066阻断JAK 2/STAT 3信号传导的激活否定了TROP 2过表达的作用。此外，作为JAK 2/STAT 3信号传导的有效激活剂的外源性IL-6能够拯救TROP 2沉默的胶质母细胞瘤细胞中JAK 2和STAT 3的磷酸化，并调节这些细胞中的表型变化。因此，我们揭示了一种新的机制，TROP 2激活JAK 2/STAT 3通路，以促进胶质母细胞瘤细胞的生长和转移。这些数据提供了对TROP 2在胶质母细胞瘤中的功能的深入了解，并表明TROP 2是胶质母细胞瘤患者的有希望的生物标志物和治疗靶点。
Trophoblast cell surface antigen 2 (TROP2), a single transmembrane domain protein, is often found to be highly expressed in various types of human cancers. However, the biological function and molecular mechanism of TROP2 in glioblastoma have not been fully elucidated, particularly in regards to cell proliferation and metastasis of glioblastoma cells. In the present study, it was demonstrated that TROP2 expression was increased in glioblastoma tissues and glioblastoma cell lines by immunohistochemical analysis and western blot analysis. High TROP2 expression was significantly correlated with the poor survival of glioblastoma patients. MTT assay, BrdU incorporation assay, flow cytometry and Transwell assay were performed to demonstrate that knockdown of TROP2 in glioblastoma cells inhibited cell proliferation and metastasis. We found that the effects of TROP2-knockdown on glioblastoma cells were associated with the inhibition of JAK2 and STAT3 phosphorylation and decreased transcription of STAT3 target genes. In addition, blocking the activation of JAK2/STAT3 signaling by WP1066 negated the effects of TROP2 overexpression. Furthermore, exogenous IL-6, which functions as a potent activator of JAK2/STAT3 signaling, was able to rescue the phosphorylation of JAK2 and STAT3 in TROP2-silenced glioblastoma cells and regulate phenotypic changes in these cells. Therefore, we revealed a novel mechanism by which TROP2 activates the JAK2/STAT3 pathway to promote the growth and metastasis of glioblastoma cells. These data offer insight into the function of TROP2 in glioblastoma and indicate that TROP2 is a promising biomarker and therapeutic target for glioblastoma patients.
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影响因子：
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