Abstract
Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that D133p53b, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. D133p53b 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 D133p53b expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were positively regulated by D133p53b 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 D133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that D133p53b 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 D133p53b isoform.