Scientists from France have identified a TP53 spliceosome which could positively regulate SOX2, OCT3/4 , NANOG, and other pluripotency key factors that promote cancer stem cell’s pluripotency. Then, it could increase the risk of cancer recurrence. The study was published in Stem Cell Report.
The p53 functions are ubiquitously altered in cancer cells by mutations/perturbation of its signaling pathways, and loss of p53 activity is a prerequisite for cancer development. Many reports have documented a p53 role in stem cell homeostasis and pluripotency. Wild-type (WT) p53 counteracts somatic cell reprogramming, whereas mutant p53 stimulates induced pluripotent stem (iPS) cell formation.
The p53 isoforms modify p53 transcriptional activity in many processes, such as cell-cycle progression, programmed cell death, replicative senescence, cell differentiation, vial replication, and angiogenesis. p53 isoforms are specifically deregulated in human tumors. However, the functions of p53 isoforms in cancer stem cell(CSC) homeostasis have never been explored.
In this study, researchers show that Δ133p53β isoform is specifically involved in promoting cancer cells stemness. Overexpression of Δ133p53β in human breast cancer cell lines stimulated mammosphere formation and the expression of key pluripotency and stemness regulators, but nor C-MYC. Furthermore, using MDA-MB-231-based cell lines, they show that increased expression of Δ133p53 isoforms correlates with the increased metastatic potential and with mammosphere formation. Finally, incubation of MCF-7 and MDA-MB-231 cells with the anti-cancer drug etoposide also promoted cell stemness in aΔ133p53-dependent manner.
Their results demonstrate that short p53 isoforms positively regulate CSC potential regardless of any p53 mutation. Consequently, WT TP53, which is considered a tumor suppressor gene, also can act as an oncogene through Δ133p53 expression.
Arsic N, Gadea G, Lagerqvist E L, et al. The p53 Isoform Δ133p53β Promotes Cancer Stem Cell Potential[J]. Stem Cell Reports, 2015.