Strong p53 Phenotypes & Potential Targets in Telomerase-Immortalized Human Cells | Oncotarget

Oncotarget #published this #research paper on February 18, 2025 in Volume 16, entitled “Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells" by researchers from the Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Cellular and Molecular Medicine Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD. ‪@JohnsHopkinsMedicine‬
#cancer #p53 #cells #oncology #paperspotlight #researchpaper #openaccess #openscience #peerreview #journal #publication #publishing #meded

DOI - https://doi.org/10.18632/oncotarget.2...

Correspondence to - Fred Bunz - [email protected]

Abstract

Cancers that retain wild type TP53 presumably harbor other clonal alterations that permitted their precursors to bypass p53-mediated growth suppression. Consequently, studies that employ TP53-wild type cancer cells and their isogenic derivatives may systematically fail to appreciate the full scope of p53 functionality. Several TP53 phenotypes are known to be absent in the widely used isogenic HCT116 colorectal cancer (CRC) model, which originated from a tumor that had retained wild type TP53. In contrast, we show that restoration of p53 in the TP53-mutant CRC cell line DLD-1 impeded cell proliferation, increased levels of senescence and sensitized cells to ionizing radiation (IR). To study p53 in a non-cancer context, we disrupted TP53 in hTERT-RPE1 cells. Derived from primary cells that were immortalized in vitro, hTERT-RPE1 expressed striking p53-dependent phenotypes and appeared to select for p53 loss during routine culture. hTERT-RPE1 expressed a p53-responsive transcriptome that was highly representative of diverse experimental systems. We discovered several novel downstream p53 targets of potential clinical relevance including ALDH3A1, which is involved in the detoxification of aldehydes and the metabolism of reactive oxygen species, and nectin cell adhesion molecule 4 (NECTIN4) which encodes a secreted surface protein that is overexpressed in many tumors.

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Keywords - cancer, p53, ionizing radiation, immortalized cells, ALDH3A1, NECTIN4

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