期刊
FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.554787
关键词
TRIM37; pancreatic cancer; phosphatase and tensin homolog; stemness; chemoresistance
类别
资金
- National Natural Science Foundation of China [81672906, 81560477, 81660483, 81860505, 81860506]
- Project of Graduate Research Fund of Guizhou Province [Qianjiaohe YJSCXJH (2019) 072, Qiankehe Pingtairencai [2016] 5647, Qiankehe Pingtairencai [2017] 5404, Qianshengzhuanhezi [2012] 94, Qianjiaoyanhe GZS [2016] 09]
Purpose The tripartite motif-containing family member TRIM37 is involved in a number of important biological and pathological processes, and it has recently been shown to be an essential regulator of protein ubiquitination and a contributor to tumorigenesis. We previously showed that TRIM37 is overexpressed in and promotes the proliferation and invasion of pancreatic cancer (PC). Methods Sphere formation, flow cytometric, qRT-PCR, western blot, colony formation, EdU incorporation, mouse xenograft model, TUNEL and IHC assays were performed to detect the role of TRIM37 in stemness and chemoresistance of PC in vitro and in vivo. Bioinformatics analysis and dual-luciferase reporter assays were used to determine which intracellular pathways might mediate the effects of TRIM37 in PC cells. Immunofluorescent(IF) staining, co-immunoprecipitation(CO-IP), protein stability and ubiquitination assays were performed to investigate the relationship between TRIM37 and PTEN. Results TRIM37 modulates the ubiquitination and degradation of the tumor suppressor phosphatase and tensin homolog (PTEN), which negatively regulates the AKT-GSK-3 beta-beta-catenin signaling pathway, thereby sustaining aberrant activation of PC cells. High expression of TRIM37 combined with low expression of PTEN correlates with poor survival of PC patients. Conclusions Collectively, our results suggest that inhibition of the TRIM37-AKT-GSK-3 beta-beta-catenin axis may be a promising strategy for treatment of PC.
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