The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer
Open accessAbstract
The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protein nestin in an Sp1/3 transcription-factor-dependent manner and that Nestin is required for tumor initiation in vivo. Moreover, loss of p53 facilitates dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells, which are poised to differentiate into hepatocellular carcinomas (HCCs) or cholangiocarcinomas (CCs) in response to lineage-specific mutations that target Wnt and Notch signaling, respectively. Many human HCCs and CCs show elevated nestin expression, which correlates with p53 loss of function and is associated with decreased patient survival. Therefore, transcriptional repression of Nestin by p53 restricts cellular plasticity and tumorigenesis in liver cancer.
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“NF-Y77 and Sp178, 79 are the coactivators most commonly linked to p53-dependent gene downregulation through a mechanism of p53 interference.”
From Census and evaluation of p53 target genes (2017) · cites this paper as [79]
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Metadata
- Authors
- Tschaharganeh, D. F., Xue, W., Calvisi, D. F., Evert, M., Michurina, T. V., Dow, L. E., Banito, A., Katz, S. F., Kastenhuber, E. R., Weissmueller, S., Huang, C.-H., Lechel, A., Andersen, J. B., Capper, D., Zender, L., Longerich, T., Enikolopov, G., & Lowe, S. W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Cold Spring Harbor Laboratory (US)
- Universitätsmedizin Greifswald (DE)
- Universität Ulm (DE)
- University of Copenhagen (DK)
- German Cancer Research Center (DE)
- University Hospital Heidelberg (DE)
- Corresponding author
- Lowe, Scott W.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 158
- Issue
- 3
- Pages
- 579-592
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4221237
- OpenAlex
- W1980168406
- Cited by
- 227
- References
- 60
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 15 · 2023: 22 · 2022: 21 · 2021: 25 · 2020: 21 · 2019: 24 · 2018: 23 · 2017: 15 · 2016: 20 · 2015: 11 · 2014: 6
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-06-02)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5p30ca045508-35)
- National Cancer Institute (P01CA087497, P30-CA045508, P01CA013106, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- p53, nestin, hepatocellular carcinoma, cholangiocarcinoma, liver cancer, cellular plasticity, dedifferentiation, progenitor-like cells, Wnt signaling, Notch signaling, tumor suppression, transcriptional repression, patient survival
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Prognosis, Transcription, Genetic, Tumor Suppressor Protein p53, Sp1 Transcription Factor, Hepatocytes, Mice, Sp3 Transcription Factor, Nestin
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