当前位置: X-MOL 学术Cell. Signal. › 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.)
Phosphorylation at Ser10 triggered p27 degradation and promoted gallbladder carcinoma cell migration and invasion by regulating stathmin1 under glucose deficiency
Cellular Signalling ( IF 4.8 ) Pub Date : 2021-01-12 , DOI: 10.1016/j.cellsig.2021.109923
Jiwen Wang 1 , Xiaojian Ni 1 , Sheng Shen 1 , Dexiang Zhang 2 , Xiaoling Ni 1 , Tao Suo 1 , Pinxiang Lu 2 , Kun Fan 3 , Han Liu 1 , Houbao Liu 1
Affiliation  

Gallbladder carcinoma (GBC) is a considerable challenge because of its high metastatic potential. The tumor microenvironment is characterized by nutrient starvation, which promotes tumor metastasis. Stathmin1, an important microtubuleregulating protein, is overexpressed and promotes metastasis in GBC. It remains unclear how the harsh tumor microenvironment regulates stathmin1 expression to affect GBC metastasis. We employed glucose deficiency to mimic nutrient starvation and found that glucose deficiency upregulated stathmin1 transcription. However, glucose deficiency also promoted p27 degradation. There was a significant negative correlation between stathmin1 and p27 protein levels under glucose deficiency. Further study revealed that, under glucose deficiency, human kinase interacting with stathmin (hKIS) induced phosphorylation at Ser10 of p27 and its translocation to the cytoplasm for degradation, which upregulated the transcription factor E2F1 to promote stathmin1 transcription. hKIS knockdown significantly inhibited p27 cytoplasmic translocation and its consequent degradation. Stathmin1 knockdown significantly inhibited GBC cell migration and invasion in vitro. Our study revealed the role of the hKIS/p27/E2F1 axis in upregulating stathmin1 transcription to promote GBC cell migration and invasion under glucose deficiency conditions



中文翻译:

Ser10 的磷酸化触发 p27 降解并通过在葡萄糖缺乏下调节 stathmin1 促进胆囊癌细胞迁移和侵袭

胆囊癌 (GBC) 是一个相当大的挑战,因为它具有很高的转移潜力。肿瘤微环境以营养缺乏为特征,促进肿瘤转移。Stathmin1 是一种重要的微管调节蛋白,在 GBC 中过表达并促进转移。目前尚不清楚严酷的肿瘤微环境如何调节 stathmin1 表达以影响 GBC 转移。我们使用葡萄糖缺乏来模拟营养缺乏,发现葡萄糖缺乏上调了 stathmin1 转录。然而,葡萄糖缺乏也促进了 p27 的降解。葡萄糖缺乏时 stathmin1 和 p27 蛋白水平呈显着负相关。进一步的研究表明,在葡萄糖缺乏的情况下,人类激酶与 stathmin (hKIS) 相互作用诱导 p27 的 Ser10 磷酸化及其易位至细胞质降解,从而上调转录因子 E2F1 以促进 stathmin1 转录。hKIS 敲低显着抑制 p27 细胞质易位及其随后的降解。Stathmin1敲低显着抑制GBC细胞迁移和侵袭体外。我们的研究揭示了 hKIS/p27/E2F1 轴在上调 stathmin1 转录以促进葡萄糖缺乏条件下 GBC 细胞迁移和侵袭中的作用

更新日期:2021-01-20
down
wechat
bug