p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer

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. (July 2014) p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer. Cell, 158 (3). pp. 579-92. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/25083869
DOI: 10.1016/j.cell.2014.05.051

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.

Item Type: Paper
Subjects: diseases & disorders > cancer > cancer types > liver cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > nestin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Enikopolov lab
CSHL labs > Lowe lab
Watson School > Publications
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 31 July 2014
Date Deposited: 08 Aug 2014 17:02
Last Modified: 16 Oct 2015 15:39
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30671

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