Centre National de la Recherche Scientifique, UMR 5237, Centre de Recherche en Biochimie Macromoléculaire, Université Montpellier, 1919 route de Mende, 34293 Montpellier Cedex 5, France.
Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle, Institut National de la Santé et de la Recherche Médicale, U661, Université Montpellier, route de Cardonille, 34094 Montpellier, France.
Stem Cell Reports. 2015 Apr 14;4(4):531-40. doi: 10.1016/j.stemcr.2015.02.001. Epub 2015 Mar 5.
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 Δ133p53β isoform.
肿瘤干细胞（CSC）是导致癌症化疗耐药和转移形成的原因。在这里，我们报告Δ133p53β（TP53 的剪接变异体）可增强 MCF-7 乳腺癌细胞的癌细胞干性，而其缺失则会降低癌细胞干性。Δ133p53β 可刺激关键多能性因子 SOX2、OCT3/4 和 NANOG 的表达。同样，在高度转移性乳腺癌细胞中，侵袭性与增强的 CSC 潜能和Δ133p53β 表达相关。与在 MCF-7 细胞中一样，Δ133p53β 也可正向调节这些细胞中 SOX2、OCT3/4 和 NANOG 的表达。最后，用细胞毒性抗癌药物依托泊苷处理 MCF-7 细胞，可通过 Δ133p53β 增加 CSC 的形成和 SOX2、OCT3/4 和 NANOG 的表达，从而增加癌症复发的风险。我们的研究结果表明，Δ133p53β 支持 CSC 潜能。此外，这些结果还表明，TP53 基因（被认为是主要的肿瘤抑制基因）也可通过 Δ133p53β 异构体发挥致癌基因的作用。
