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The p53 isoform ?133p53? promotes cancer stem cell potential.


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

SUBMITTER: Arsic N 

PROVIDER: S-EPMC4400643 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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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, an  ...[more]

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