TRIM47 accelerates aerobic glycolysis and tumor progression through regulating ubiquitination of FBP1 in pancreatic cancer
TRIM47 accelerates aerobic glycolysis and tumor progression through regulating ubiquitination of FBP1 in pancreatic cancer
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TRIM47 通过调节胰腺癌中 FBP1 的泛素化来加速有氧糖酵解和肿瘤进展
DOI：
10.1016/j.phrs.2021.105429
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发表时间：
2021-02-17
影响因子：
9.3
通讯作者：
Yang, Ming
中科院分区：
文献类型：
--
作者：
Li, Lei;Yu, Yuan;Yang, Ming
越来越多的研究表明，泛素化在胰腺癌的发病机制中起着至关重要的作用，靶向调控泛素化过程是一种潜在的肿瘤治疗手段。然而，三重基序47（TRIM 47）在胰腺癌中的作用仍不清楚。在这里，在胰腺癌患者组织中发现TRIM 47表达显着上调和FBP 1表达下降，这表明生存率较低。此外，我们发现TRIM 47在胰腺癌细胞中上调，并在体外和体内促进细胞增殖。TRIM 47促进胰腺癌细胞有氧糖酵解的机制研究表明，TRIM 47促进胰腺癌细胞有氧糖酵解主要依赖于与果糖-1，6-二磷酸酶（FBP 1）的直接结合和泛素化。此外，TRIM 47对瓦尔堡效应和胰腺癌进展的促进作用被FBP 1的过表达消除。因此，靶向TRIM 47/FBP 1轴可能提供抑制胰腺癌发展的新策略。
Increasing studies demonstrated that ubiquitination plays a vital role in the pathogenesis of pancreatic cancer, and targeting regulation of the ubiquitination process is a potential means for cancer treatment. However, the role of tripartite motif 47 (TRIM47) in pancreatic cancer is still unclear. Here, significantly upregulated TRIM47 and decreased FBP1 expressions were found in pancreatic cancer patient tissues and pointed to a lower survival rate. In addition, we show that TRIM47 was upregulated in pancreatic cancer cells and promoted cell proliferation in vitro and in vivo. Mechanistic investigations showed that TRIM47 promoted the aerobic glycolysis of pancreatic cancer cells, which was largely dependent on the direct binding to and ubiquitination of fructose-1, 6-biphosphatase (FBP1). Furthermore, the promotion of TRIM47 on the Warburg effect and pancreatic cancer progression was abolished by the overexpression of FBP1. Therefore, targeting TRIM47/FBP1 axis might provide a novel strategy to suppress the development of pancreatic cancer.