The p53 Isoform Δ133p53β Promotes Cancer Stem Cell Potential

Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Delta 133p53 beta, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. Delta 133p53 beta 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 Delta 133p53 beta expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were positively regulated by Delta 133p53 beta 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 Delta 133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that Delta 133p53 beta 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 Delta 133p53 beta isoform.