The p53 isoform Δ133p53β promotes cancer stem cell potential

Abstract

Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Δ133p53β, a TP53 splice variant, enhanced cancer cell stemneß in MCF-7 breast cancer cells, while its depletion reduced it. Δ133p53β stimulated the expreßion of the key pluripotency factors SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells, aggreßiveneß was coupled with enhanced CSC potential and Δ133p53β expreßion. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expreßion were positively regulated by Δ133p53β in these cells. Finally, treatment of MCF-7 cells with etoposide, a cytotoxic anti-cancer drug, increased CSC formation and SOX2, OCT3/4, and NANOG expreßion via Δ133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that Δ133p53β supports CSC potential. Moreover, they indicate that the TP53 gene, which is considered a major tumor suppreßor gene, also acts as an oncogene via the Δ133p53βb isoform.