p53-dependent nestin regulation links tumor suppression to cellular plasticity in liver cancer Journal Article


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.
Article Title: p53-dependent nestin regulation links tumor suppression to cellular plasticity in liver cancer
Abstract: 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. © 2014 Elsevier Inc.
Keywords: adult; cancer survival; controlled study; human tissue; protein expression; gene mutation; human cell; liver cell carcinoma; nonhuman; animal cell; mouse; animal tissue; animal experiment; animal model; notch receptor; cell differentiation; protein p53; cell lineage; cancer inhibition; tumor suppressor gene; gene repression; cancer stem cell; transcription factor sp1; gene loss; bile duct carcinoma; liver cell; malignant transformation; nestin; wnt protein; transcription termination; cell dedifferentiation; liver carcinogenesis; wnt signaling pathway; cancer prognosis; human; female; priority journal; article; transcription factor sp3
Journal Title: Cell
Volume: 158
Issue: 3
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2014-07-31
Start Page: 579
End Page: 592
Language: English
DOI: 10.1016/j.cell.2014.05.051
PROVIDER: scopus
PUBMED: 25083869
PMCID: PMC4221237
DOI/URL:
Notes: Cited By (since 1996):1 -- Export Date: 2 September 2014 -- CODEN: CELLB -- Source: Scopus
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