CDK4/6 抑制剂 PD0332991 通过抑制 MAGED1 的表达稳定 FBP1 在胰腺导管腺癌中的表达。

The CDK4/6 inhibitor PD0332991 stabilizes FBP1 by repressing MAGED1 expression in pancreatic ductal adenocarcinoma.

机构信息

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Hand Surgery, West Campus, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Int J Biochem Cell Biol. 2020 Nov;128:105859. doi: 10.1016/j.biocel.2020.105859. Epub 2020 Sep 25.

DOI:10.1016/j.biocel.2020.105859

PMID:32987196

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly solid tumors in the world. Aerobic glycolysis is among the characteristic features of pancreatic cancer. However, the regulatory process of aerobic glycolysis in pancreatic cancer is too complicated, and the underlying mechanism remains unexplained. Reportedly, CDK4/6 inhibitors repress breast cancer cell proliferation by modulating glucose metabolism. Here, we reveal that the CDK4/6 inhibitor, PD0332991 stabilized FBP1 to hinder aerobic glycolysis in pancreatic cancer. We also show that the CDK4/6-E2 F1 signaling pathway mediated an increase in MAGED1 expression, promoting FBP1 degradation in pancreatic cancer. We, therefore, might have identified a novel mechanism by which the CDK4/6 inhibitor, PD0332991 blocks the Warburg effect of pancreatic cancer by stabilizing FBP1.

摘要

胰腺导管腺癌（PDAC）是世界上最致命的实体肿瘤之一。有氧糖酵解是胰腺癌的特征之一。然而，胰腺癌中有氧糖酵解的调节过程过于复杂，其潜在机制尚不清楚。据报道，CDK4/6 抑制剂通过调节葡萄糖代谢来抑制乳腺癌细胞的增殖。在这里，我们揭示 CDK4/6 抑制剂 PD0332991 通过稳定 FBP1 来抑制胰腺癌细胞中的有氧糖酵解。我们还表明，CDK4/6-E2 F1 信号通路介导 MAGED1 表达增加，促进胰腺癌细胞中 FBP1 的降解。因此，我们可能已经确定了一种新的机制，即 CDK4/6 抑制剂 PD0332991 通过稳定 FBP1 来阻断胰腺癌细胞的瓦博格效应。