Posted: Wednesday, May 11, 2022
According to Xin Xie, MD, of Shanghai Jiaotong University, China, and colleagues, TRIM38 (a protein coding gene of tripartite motif-containing 38) seems to act as a suppressor of bladder cancer pathogenesis. The results of this study, which were published in the Journal of Translational Medicine, suggest the TRIM38/glucose transporter type 1 (GLUT1) axis may be a therapeutic vulnerability for clinical treatment.
“Taken together, our results revealed that TRIM38 is an E3 ubiquitin ligase for GLUT1 and mediates GLUT1 ubiquitination and degradation,” the investigators commented. “TRIM38 inhibition enhances bladder cancer malignant features, including cell growth, migration, and glycolysis capacity.”
The investigators examined the functional roles of TRIM38 in bladder cancer through in vitro and in vivo experiments. A list of ubiquitination-associated signatures was generated using screening data from the bladder cancer cohort of The Cancer Genome Atlas. Based on subsequent validations, TRIM38 seemed to be a significant tumor suppressor; the expression levels of this gene were found to be low in bladder cancer. The Kaplan-Meier and correlation analyses revealed that patients with low TRIM38 expression levels had shorter durations of survival and advanced clinical characteristics. Targeting TRIM38 seemed to enhance bladder cancer cell proliferation, migration, and stemness.
TRIM38 was found to interact with GLUT1, which seemed to promote its ubiquitinoylation and degradation. According to the investigators, TRIM38 deficiency relied on accumulated GLUT1 proteins to enhance malignant features and cellular glycolytic capacity. The efficacy of BAY-876 was investigated in bladder cancer, and the half maximal inhibitory concentrations of this GLUT1 inhibitor were determined across cell lines. Experiments using tumor xenograft models suggested that BAY-876 may effectively suppress the in vivo growth of TRIM38-low and TRIM38-negative bladder cancer.
Disclosure: The study authors reported no conflicts of interest.
Journal of Translational Medicine