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Caron de Fromentel et al. Hepatoma Res 2020;6:80 Hepatoma Research
DOI: 10.20517/2394-5079.2020.77

Review Open Access

p53 functional loss, stemness and hepatocellular
carcinoma

Claude Caron de Fromentel , Massimo Levrero 1,2,3,4
1
1 Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Université Claude Bernard Lyon 1, Centre Léon
Bérard, Lyon 69008, France.
2 Service d’Hépatologie et de Gastroentérologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon 69004, France.
3 Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari (SCIAC), Sapienza University, Rome 00161,
Italy.
4 Center for Life Nano Science, Istituto Italiano di Tecnologia, Sapienza University, Rome 00161, Italy.
Correspondence to: Dr. Claude Caron de Fromentel, team «Epigenetics, microenvironment and liver cancer», Centre de Recherche
en Cancérologie de Lyon, INSERM U1052, 151 cours Albert Thomas, Lyon 69003, France. E-mail: claude.de-fromentel@inserm.fr
How to cite this article: Caron de Fromentel C, Levrero M. p53 functional loss, stemness and hepatocellular carcinoma. Hepatoma
Res 2020;6:80. http://dx.doi.org/10.20517/2394-5079.2020.77
Received: 7 Aug 2020 First Decision: 10 Sep 2020 Revised: 22 Sep 2020 Accepted: 29 Sep 2020 Published: 6 Nov 2020

Academic Editors: Anne Corlu, Orlando Musso Copy Editor: Cai-Hong Wang Production Editor: Jing Yu
Received: First Decision: Revised: Accepted: Published:

Science Editor: Copy Editor: Production Editor: Jing Yu Abstract
The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63
and p73, the two other members of the p53 family. Loss of functional p53 leads to the proliferation and survival
of mature cells and progenitor or stem cells that accumulate genetic alterations, thus favoring tumorigenesis. p53
loss of function, observed in a wide variety of human tumor types, is frequently caused by missense mutations
more frequently found in the DNA binding domain, but can also be due to the expression of a plethora of viral and
cellular negative regulators. Human hepatocellular carcinoma (HCC) represents a specific situation, first because
the TP53 gene mutations pattern exhibits a “hot spot” rarely found in other tumor types that is linked to Aflatoxin
B1 exposure and, second, because many HCCs do not exhibit any TP53 mutation. Here, we provide an overview of
the current knowledge about the inhibition of p53 functions by the N-terminal (ΔN) truncated forms of the family,
and their role in the emergence and maintenance of pre-malignant cells with stem cell characteristics and in HCC
development. We focus in particular on the Nanog-IGF1R-ΔNp73 axis that is associated with stem-like features in
HCC cells and that may provide an attractive new therapeutic target and help to develop new biomarkers for HCC
risk stratification, as well as preventive strategies.

Keywords: p53 family, p53 functional inactivation, ΔNp73, hepatic progenitor cells, cancer stem cells, Nanog,
hepatocellular carcinoma

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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