Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Pharmacol Res. 2021 Apr;166:105429. doi: 10.1016/j.phrs.2021.105429. Epub 2021 Jan 30.
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.
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，靶向调节泛素化过程是癌症治疗的一种潜在手段。然而，TRIM47 在胰腺癌中的作用尚不清楚。在这里，我们发现 TRIM47 在胰腺癌患者组织中显著上调，而 FBP1 的表达下调，这与较低的生存率相关。此外，我们还表明 TRIM47 在胰腺癌细胞中上调，并促进体外和体内的细胞增殖。机制研究表明，TRIM47 促进了胰腺癌细胞的有氧糖酵解，这在很大程度上依赖于其与果糖-1,6-二磷酸酶（FBP1）的直接结合和泛素化。此外，通过过表达 FBP1 可以消除 TRIM47 对瓦博格效应和胰腺癌进展的促进作用。因此，靶向 TRIM47/FBP1 轴可能为抑制胰腺癌的发展提供一种新策略。
