SOX2 Is a Marker for Stem-like Tumor Cells in Bladder Cancer

Abstract

Summary: It has been reported that functionally distinct cancer stem cells (CSCs) exist in human bladder cancer (BCa). Here, we found that Sox2, a transcription factor that is well characterized as a marker for stem cells, is upregulated in both mouse and human BCa. Sox2 expression is absent in normal urothelial cells, but it begins to be expressed in pre-neoplastic bladder tumors and continues to be expressed in invasive mouse BCa. Using s as a reporter of Sox2 transcriptional expression, we demonstrated that Sox2-expressing cells mark a subpopulation of tumor cells that fuel the growth of established BCa. SOX2-positive cells also expressed other previously reported BCa CSC markers, including Keratin14 (KRT14) and CD44v6. Ablation of Sox2-expressing cells within primary invasive BCa led to enhanced tumor regression, supporting the essential role of SOX2-positive cells in regulating BCa maintenance and progression. Our data show that Sox2 is a marker of bladder CSCs and indicate it as a potential clinical target for BCa therapy. : In this article, Yang and colleagues assess the renewal and differentiation potential of Sox2-expressing cells in bladder cancer, by in vitro clonogenic assays, in vivo transplantation, and lineage-tracing experiments. Their data indicate that Sox2 expression marks the bladder cancer stem cells, which are necessary for tumor growth and maintenance. Keywords: bladder cancer, Sox2, cancer stem cell