Loss of the SxxSS motif in a human T-cell factor-4 isoform confers hypoxia resistance to liver cancer: an oncogenic switch in Wnt signaling.

ABSTRACT:

Purpose

Aberrantly activated Wnt/β-catenin signaling is important in hepatocellular carcinoma (HCC) development. Downstream gene expressions involving the Wnt/β-catenin cascade occur through T-cell factor (TCF) proteins. Here, we show the oncogenic potential of human TCF-4 isoforms based on the expression of a single conserved SxxSS motif.

Methods

We investigated the TCF-4J and K isoform pair characterized by the presence (K) or absence (J) of the SxxSS motif. The mRNA expression profiles were examined in 47 pairs of human HCCs and adjacent non-cancerous liver tissues by RT-PCR. Proliferation, sphere assays and immunoblot analysis were performed under normoxia and hypoxia conditions. The ability of HCC cells overexpressing TCF-4J (J cells) and K (K cells) to grow as solid tu

SUBMITTER: Koga H 

PROVIDER: S-EPMC3386968 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature