Press Release
Tumor cells containing the African-Centric S47 variant of TP53 show increased Warburg metabolism
FOR IMMEDIATE RELEASE
We recently reported that S47 tumor cells are resistant to the majority of cytotoxic chemotherapeutic agents, but show increased sensitivity to a subset of anti-cancer agents, compared to tumors with WT p53.
We find that S47 tumors show decreased mitochondrial metabolism, along with increased dependency on glycolysis.
S47 tumor cells also show increased sensitivity to the glycolytic poison 2-deoxy-glucose.
"The TP53 tumor suppressor plays a critical role in suppressing tumorigenesis by directly regulating the expression of genes that promote apoptosis, cell cycle arrest, and senescence."
Cancer stem cells, also called tumor-initiating cells, drive tumorigenesis and tumor heterogeneity through their abilities to self-renew and generate tumorigenic progeny.
For instance, TAZ confers self-renewal capacity, a CSC property, on breast, brain, and oral cancer cells, probably by inducing the EMT.
Similarly, YAP confers some CSC properties, such as sphere formation and chemoresistance, on hepatocellular carcinoma, esophageal cancer, osteosarcoma, and basal-like breast cancer cells by coordinating the expression of interleukin 6 and stemness marker proteins such as SOX2, SOX9, and CD90.
Nevertheless, the biological roles of LATS1/2, as well as the mechanisms by which they enable cancer cells to acquire and maintain CSC properties, are incompletely understood.
In this study, using SAS cells as a model of CSCs in OSCC, we showed that LATS1/2 are essential for self-renewal of CSCs, and in particular for the initiation of sphere formation.
"In addition to mutations, there are single nucleotide polymorphisms in TP53 that dampen p53 function, and that can increase cancer risk and decrease the efficacy of cancer therapy."
Full text - https://doi.org/10.18632/oncotarget.26660
Correspondence to - Maureen E. Murphy - mmurphy@wistar.org
Keywords - p53, Pro47Ser, metabolism, RRAD, mitochondria
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