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] |
---|
Links: |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM285391178 | ||
003 | DE-627 | ||
005 | 20231225045338.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2018 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.ccell.2018.05.003 |2 doi | |
028 | 5 | 2 | |a pubmed24n0951.xml |
035 | |a (DE-627)NLM285391178 | ||
035 | |a (NLM)29894692 | ||
035 | |a (PII)S1535-6108(18)30217-4 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Dhar, Debanjan |e verfasserin |4 aut | |
245 | 1 | 0 | |a Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling |
264 | 1 | |c 2018 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 24.05.2019 | ||
500 | |a Date Revised 08.04.2022 | ||
500 | |a published: Print | ||
500 | |a CommentIn: Trends Cancer. 2018 Sep;4(9):602-605. - PMID 30149877 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2018 Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CD44 | |
650 | 4 | |a DNA damage response | |
650 | 4 | |a EGFR | |
650 | 4 | |a HCC | |
650 | 4 | |a MDM2 nuclear translocation | |
650 | 4 | |a cancer initiation | |
650 | 4 | |a hepatocellular carcinoma | |
650 | 4 | |a liver cancer | |
650 | 4 | |a p53 | |
650 | 4 | |a p53 termination | |
650 | 7 | |a Hyaluronan Receptors |2 NLM | |
650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
700 | 1 | |a Antonucci, Laura |e verfasserin |4 aut | |
700 | 1 | |a Nakagawa, Hayato |e verfasserin |4 aut | |
700 | 1 | |a Kim, Ju Youn |e verfasserin |4 aut | |
700 | 1 | |a Glitzner, Elisabeth |e verfasserin |4 aut | |
700 | 1 | |a Caruso, Stefano |e verfasserin |4 aut | |
700 | 1 | |a Shalapour, Shabnam |e verfasserin |4 aut | |
700 | 1 | |a Yang, Ling |e verfasserin |4 aut | |
700 | 1 | |a Valasek, Mark A |e verfasserin |4 aut | |
700 | 1 | |a Lee, Sooyeon |e verfasserin |4 aut | |
700 | 1 | |a Minnich, Kerstin |e verfasserin |4 aut | |
700 | 1 | |a Seki, Ekihiro |e verfasserin |4 aut | |
700 | 1 | |a Tuckermann, Jan |e verfasserin |4 aut | |
700 | 1 | |a Sibilia, Maria |e verfasserin |4 aut | |
700 | 1 | |a Zucman-Rossi, Jessica |e verfasserin |4 aut | |
700 | 1 | |a Karin, Michael |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cancer cell |d 2002 |g 33(2018), 6 vom: 11. Juni, Seite 1061-1077.e6 |w (DE-627)NLM119589826 |x 1878-3686 |7 nnns |
773 | 1 | 8 | |g volume:33 |g year:2018 |g number:6 |g day:11 |g month:06 |g pages:1061-1077.e6 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ccell.2018.05.003 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 33 |j 2018 |e 6 |b 11 |c 06 |h 1061-1077.e6 |