Defining the Role of Beta-Catenin Activation in Wilms Tumor
Abstract
Wilms tumor (WT) resembles the developing kidney, consisting of blastema/nephron progenitor cells (NPCs), epithelium, and stoma-indicating a link between the dysregulation of normal development and tumorigenesis. While activation of beta-catenin has been shown in a significant proportion of WTs, much remains to be understood about its role in tumor development. Previously, it has been assumed that NPCs act as a cancer stem cell; however, mouse models with activation of beta-catenin within the NPC lineage paradoxically show premature loss of blastema, a phenotype opposite to WT. Given that we and others have shown that disrupting signals from developing renal stroma results in abnormally maintained NPCs (reminiscent of WT nephrogenic rests), we hypothesized that signaling from the stroma, specifically activation of beta-catenin, contributes to Wilms tumorigenesis. Indeed, we have shown that activation of beta-catenin in stromal progenitors inhibits NPC differentiation. Additionally, comparisons of the transcriptomes from human WT to mutant mouse kidneys with beta-catenin activation in the stromal vs NPC lineages revealed that human WT more closely resembled stromal mutants, suggesting that stromal beta-catenin activation results in histological and molecular features of WT. Future studies will assess mechanisms of stromal-NPC crosstalk, both in normal development and human Wilms tumor samples.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1119464
Entities
People
- Keri Drake
Organizations
- University of Texas at Austin