Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling

Copyright © 2018 Elsevier Inc. All rights reserved..

How fully differentiated cells that experience carcinogenic insults become proliferative cancer progenitors that acquire multiple initiating mutations is not clear. This question is of particular relevance to hepatocellular carcinoma (HCC), which arises from differentiated hepatocytes. Here we show that one solution to this problem is provided by CD44, a hyaluronic acid receptor whose expression is rapidly induced in carcinogen-exposed hepatocytes in a STAT3-dependent manner. Once expressed, CD44 potentiates AKT activation to induce the phosphorylation and nuclear translocation of Mdm2, which terminates the p53 genomic surveillance response. This allows DNA-damaged hepatocytes to escape p53-induced death and senescence and respond to proliferative signals that promote fixation of mutations and their transmission to daughter cells that go on to become HCC progenitors.

Errataetall:

CommentIn: Trends Cancer. 2018 Sep;4(9):602-605. - PMID 30149877

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:33

Enthalten in:

Cancer cell - 33(2018), 6 vom: 11. Juni, Seite 1061-1077.e6

Sprache:

Englisch

Beteiligte Personen:

Dhar, Debanjan [VerfasserIn]
Antonucci, Laura [VerfasserIn]
Nakagawa, Hayato [VerfasserIn]
Kim, Ju Youn [VerfasserIn]
Glitzner, Elisabeth [VerfasserIn]
Caruso, Stefano [VerfasserIn]
Shalapour, Shabnam [VerfasserIn]
Yang, Ling [VerfasserIn]
Valasek, Mark A [VerfasserIn]
Lee, Sooyeon [VerfasserIn]
Minnich, Kerstin [VerfasserIn]
Seki, Ekihiro [VerfasserIn]
Tuckermann, Jan [VerfasserIn]
Sibilia, Maria [VerfasserIn]
Zucman-Rossi, Jessica [VerfasserIn]
Karin, Michael [VerfasserIn]

Links:

Volltext

Themen:

CD44
Cancer initiation
DNA damage response
EGFR
HCC
Hepatocellular carcinoma
Hyaluronan Receptors
Journal Article
Liver cancer
MDM2 nuclear translocation
P53
P53 termination
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Tumor Suppressor Protein p53

Anmerkungen:

Date Completed 24.05.2019

Date Revised 08.04.2022

published: Print

CommentIn: Trends Cancer. 2018 Sep;4(9):602-605. - PMID 30149877

Citation Status MEDLINE

doi:

10.1016/j.ccell.2018.05.003

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM285391178