ENC1 Promotes the Malignant Progression and Metastasis by Suppressing TRIM21 Mediated Vimentin Degradation in Wilms Tumor.

Abstract

Ectodermal neural cortex 1 (ENC1) is significantly upregulated in various cancers and shows a positive correlation with poor prognosis and advanced clinical stages, such as colorectal cancer, endometrial cancer and breast cancer. However, the role of ENC1 in Wilms tumor (WT) has not been previously reported. In this study, we conducted several in vitro functional experiments and established xenograft models to confirm the oncogenic potential of ENC1. The binding proteins of ENC1 were identified through co-immunoprecipitation and mass spectrometry to screen the mechanism of malignant progression. Further analysis elucidated the mechanism by which ENC1 promotes tumorigenesis. The results demonstrated that ENC1 was significantly overexpressed in tumor and recurrence samples, with elevated ENC1 expression showing a significant negative correlation with both overall survival and recurrence-free survival of patients. Functionally, the role of ENC1 in tumor oncogenicity was elucidated through the assessment of tumor cell proliferation, migration, and invasion capabilities. Mechanistically, through immunoprecipitation and mass spectrometry, we identified Vimentin as an interacting protein of ENC1. ENC1 competed with the E3 ubiquitin ligase TRIM21 for Vimentin binding, thereby reducing the ubiquitination level of Vimentin and enhancing its protein stability. In conclusion, this study demonstrates that ENC1 functions as a novel oncogenic target for Wilms tumor by disrupting TRIM21-mediated ubiquitination of Vimentin, which presents novel insights for the treatment of Wilms tumor and the development of prognostic markers.