Wilms6 Cells

The Wilms6 cell line was established from a primary Wilms tumor in a pediatric patient with a germline WT1 mutation. This cell line is defined by a homozygous nonsense mutation in the WT1 gene (c.1168 C>T, p.R390X), which results in a truncated and non-functional WT1 protein. WT1 is a critical regulator of kidney development, and its loss is strongly associated with Wilms tumor, particularly in cases displaying mesenchymal differentiation. The Wilms6 cell line is an important model for studying the tumorigenic effects of complete WT1 loss, particularly in the context of tumors that exhibit both epithelial and mesenchymal characteristics. Wilms6 cells also carry a mutation in the CTNNB1 gene, specifically affecting serine 45 (p.S45F), a key site for phosphorylation that regulates β-Catenin degradation. This mutation leads to the stabilization and nuclear accumulation of β-Catenin, resulting in the constitutive activation of the Wnt signaling pathway. The aberrant activation of Wnt signaling is a known driver of cell proliferation and tumorigenesis in Wilms tumors, making Wilms6 a valuable tool for investigating the role of Wnt pathway dysregulation in tumors with WT1 mutations. Phenotypically, Wilms6 cells display a mesenchymal morphology, with strong expression of vimentin and absence of epithelial markers such as cytokeratin, reflecting the stromal nature of the original tumor. These cells have been shown to possess limited but notable differentiation potential, including the ability to differentiate into muscle-like cells under specific conditions, which mirrors the mesenchymal differentiation observed in some Wilms tumors. Proteomic studies of Wilms6 have identified the activation of multiple receptor tyrosine kinases (RTKs), including PDGFRβ and AXL, which are involved in promoting cell survival, proliferation, and migration. The downstream activation of signaling pathways such as MAPK and PI3K/AKT further underscores the aggressive nature of this cell line. Overall, the Wilms6 cell line serves as a crucial model for exploring the molecular mechanisms underlying Wilms tumor development, particularly in cases of complete WT1 loss combined with Wnt signaling activation. Its genetic and phenotypic characteristics make it an excellent platform for studying the interplay between WT1 deficiency and aberrant signaling pathways, providing insights into potential therapeutic targets for this aggressive tumor type. Kidney cancer cell lines, Kidney, Wilms tumor, Growth Conditions: Adherent, Biosafety level: BSL 1