AUTHOR=Lalli Enzo TITLE=A reappraisal of transcriptional regulation by NR5A1 and beta-catenin in adrenocortical carcinoma JOURNAL=Frontiers in Endocrinology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1303332 DOI=10.3389/fendo.2023.1303332 ISSN=1664-2392 ABSTRACT=Background

Overexpression of the transcription factor NR5A1 and constitutive activation of canonical Wnt signalling leading to nuclear translocation of beta-catenin are hallmarks of malignancy in adrenocortical carcinoma (ACC). Based on the analysis of genomic profiles in H295R ACC cells, Mohan et al. (Cancer Res. 2023; 83: 2123-2141) recently suggested that a major determinant driving proliferation and differentiation in malignant ACC is the interaction of NR5A1 and beta-catenin on chromatin to regulate gene expression.

Methods

I reanalyzed the same set of data generated by Mohan et al. and other published data of knockdown-validated NR5A1 and beta-catenin target genes,

Results

Beta-catenin is mainly found in association to canonical T cell factor/lymphoid enhancer factor (TCF/LEF) motifs in genomic DNA. NR5A1 and beta-catenin regulate distinct target gene sets in ACC cells.

Conclusion

Overall, my analysis suggests a model where NR5A1 overexpression and beta-catenin activation principally act independently, rather than functionally interacting, to drive ACC malignancy.