The p53 Isoform Δ133p53β Promotes Cancer Stem Cell Potential

摘要

Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that D133p53b, a TP53splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. D133p53b stimulated theexpression of the key pluripotency factors SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells, aggressivenesswas coupled with enhanced CSC potential and D133p53b expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression werepositively regulated by D133p53b in these cells. Finally, treatment of MCF-7 cells with etoposide, a cytotoxic anti-cancer drug, increasedCSC formation and SOX2, OCT3/4, and NANOG expression via D133p53, thus potentially increasing the risk of cancer recurrence. Ourfindings show that D133p53b supports CSC potential. Moreover, they indicate that the TP53 gene, which is considered a major tumorsuppressor gene, also acts as an oncogene via the D133p53b isoform.