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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.
Pubmed ID: 29894692 RIS Download
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View all literature mentionsThis unknown targets Digoxigenin
View all literature mentionsThis unknown targets normal rabbit IgG
View all literature mentionsThis monoclonal targets Human, Mouse, Rat, Monkey
View all literature mentionsThis polyclonal targets Phospho-Stat3 (Tyr705) Antibody detects endogenous levels of Stat3 only when phosphorylated at Tyr705. The antibody does not cross-react with other Stat proteins when phosphorylated on the corresponding tyrosine residue. Does cross-react withPhospho-EGFR
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis monoclonal targets p21 waf1
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View all literature mentionsThis monoclonal targets Human PMAIP1
View all literature mentionsThis polyclonal targets Cytochrome P450 Enzyme CYP2E1
View all literature mentionsThis monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis monoclonal targets EGF Receptor
View all literature mentionsThis monoclonal targets Phospho-EGF Receptor (Tyr1068)
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473) (736E11) Rabbit mAb
View all literature mentionsThis polyclonal targets MDM2, phospho (Ser166)
View all literature mentionsThis monoclonal targets MDM2 (Ab-2) Human (Mouse)
View all literature mentionsThis unknown targets Recombinant mouse p53 protein
View all literature mentionsThis polyclonal targets Phospho-p53 (Ser15)
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View all literature mentionsThis monoclonal targets CD44
View all literature mentionsMus musculus with name C57BL/6NCrl from IMSR.
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View all literature mentionsMus musculus with name B6.Cg-Speer6-ps1Tg(Alb-cre)21Mgn/J from IMSR.
View all literature mentionsMus musculus with name B6.129S6(Cg)-Cdkn1atm1Led/J from IMSR.
View all literature mentionsMus musculus with name B6.129(Cg)-Cd44tm1Hbg/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6NCrl from IMSR.
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