TRIM37 Mediates Chemoresistance and Maintenance of Stemness in Pancreatic Cancer Cells via Ubiquitination of PTEN and Activation of the AKT–GSK-3β–β-Catenin Signaling Pathway

Abstract

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: . 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-3β-β-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-3β-β-catenin axis may be a promising strategy for treatment of PC.