当前位置: X-MOL 学术J. Cell Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
BMP4 promotes the metastasis of gastric cancer by inducing epithelial-mesenchymal transition via ID1.
Journal of Cell Science ( IF 3.3 ) Pub Date : 2020-06-11 , DOI: 10.1242/jcs.237222
Ganlu Deng 1, 2 , Yihong Chen 1, 3 , Cao Guo 1, 4 , Ling Yin 1, 3 , Ying Han 1, 3 , Yiyi Li 1, 3 , Yaojie Fu 1, 3 , Changjing Cai 1, 3 , Hong Shen 1, 3, 4 , Shan Zeng 3, 5
Affiliation  

Ganlu Deng, Yihong Chen, Cao Guo, Ling Yin, Ying Han, Yiyi Li, Yaojie Fu, Changjing Cai, Hong Shen, and Shan Zeng

Epithelial–mesenchymal transition (EMT) is a crucial process for cancer cells to acquire metastatic potential, which primarily causes death in gastric cancer (GC) patients. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β family that plays an indispensable role in human cancers. However, little is known about its roles in GC metastasis. In this study, BMP4 was found to be frequently overexpressed in GC tissues and was correlated with poor patient's prognosis. BMP4 was upregulated in GC cell lines and promoted EMT and metastasis of GC cells both in vitro and in vivo, whereas knockdown of BMP4 significantly inhibited EMT and metastasis of GC cells. Furthermore, the inhibitor of DNA binding 1 (also known as DNA-binding protein inhibitor ID1) was identified as a downstream target of BMP4 using PCR arrays and was upregulated via SMAD1/5/8 phosphorylation. ID1 knockdown attenuated BMP4-induced EMT and invasion in GC cells. Moreover, ID1 overexpression in BMP4 knockdown cells restored the promotion of EMT and cell invasion. In summary, BMP4 induced EMT and promoted GC metastasis by upregulating ID1 expression. Antagonizing BMP4 could be a potential therapeutic strategy for GC metastasis.



中文翻译:

BMP4通过ID1诱导上皮间质转化促进胃癌转移。

邓甘露、陈一红、郭曹、尹凌、韩英、李依依、付耀杰、蔡长晶、沉洪、曾山

上皮-间质转化(EMT)是癌细胞获得转移潜力的关键过程,这主要导致胃癌(GC)患者死亡。骨形态发生蛋白4(BMP4)是TGF-β家族的成员,在人类癌症中发挥着不可或缺的作用。然而,人们对其在GC转移中的作用知之甚少。在这项研究中,BMP4被发现在胃癌组织中经常过度表达,并且与患者的不良预后相关。BMP4在GC细胞系中上调,并在体外体内促进GC细胞的EMT和转移,而敲低BMP4则显着抑制GC细胞的EMT和转移。此外,使用 PCR 阵列将 DNA 结合 1 抑制剂(也称为 DNA 结合蛋白抑制剂 ID1)确定为 BMP4 的下游靶标,并通过 SMAD1/5/8 磷酸化上调。ID1 敲除减弱了 BMP4 诱导的 GC 细胞 EMT 和侵袭。此外,BMP4敲低细胞中ID1的过表达恢复了EMT和细胞侵袭的促进作用。综上所述,BMP4通过上调ID1表达诱导EMT并促进GC转移。拮抗 BMP4 可能是胃癌转移的潜在治疗策略。

更新日期:2020-06-11
down
wechat
bug