PLX179215

GSE133976: GREB1, a novel target of Wnt signaling, promotes development of hepatoblastoma by suppressing TGF signaling

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The -catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/-catenin signaling induces HB tumor formation is unknown. We found that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/-catenin signaling in HB patients. GREB1 was localized to the nucleus where it bound Smad2/3 in a competitive manner with p300 and inhibited TGF signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of -catenin, YAP, and c-Met induced HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppressed marker gene expression and HB-like liver tumorigenesis, and instead enhanced TGF signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppressed the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a novel target molecule of Wnt/-catenin signaling and required for HB progression. SOURCE: Daisuke Okuzaki (dokuzaki@biken.osaka-u.ac.jp) - Research institute for microbial diseases, Osaka university