TRIM47 accelerates aerobic glycolysis and tumor progression through regulating ubiquitination of FBP1 in pancreatic cancer

A mechanistic model showing that tripartite motif 47 (TRIM47) promotes aerobic glycolysis and pancreatic cancer growth by stimulating the ubiquitination and degradation of fructose-1, 6-biphosphatase (FBP1). [Display omitted] Increasing studies demonstrated that ubiquitination plays a vital role in...

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Bibliographic Details
Published in:Pharmacological research 2021-04, Vol.166, p.105429, Article 105429
Main Authors: Li, Lei, Yu, Yuan, Zhang, Zhengle, Guo, Yao, Yin, Tao, Wu, Heshui, Yang, Ming
Format: Article
Language:English
Subjects:
Aerobic glycolysis
Animals
Carrier Proteins - metabolism
Cell Line, Tumor
Disease Progression
FBP1
Fructose-Bisphosphatase - metabolism
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Proteins - metabolism
Nuclear Proteins - metabolism
Pancreatic cancer
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
TRIM47
Ubiquitination
Warburg Effect, Oncologic
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Summary:A mechanistic model showing that tripartite motif 47 (TRIM47) promotes aerobic glycolysis and pancreatic cancer growth by stimulating the ubiquitination and degradation of fructose-1, 6-biphosphatase (FBP1). [Display omitted] 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.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2021.105429