Aberrant β-catenin activation contributes to a third or more of human hepatocellular carcinoma (HCC), but β-catenin activation alone is not sufficient to induce liver cancer in mice.
Aberrant activation of the Wnt/β-catenin pathway is a major and frequent event in liver cancer, but inhibition of oncogenic β-catenin signaling has proven challenging.
Altogether, our study uncovers a regulatory mechanism underlying liver cancer-specific Wnt transcriptional output, and suggests that TRIB2 functions as a signaling nexus to integrate the Wnt/β-catenin, Hippo/YAP, and C/EBPα pathways in cancer cells.
BrMC can inhibit the functions and characteristics of LCSCs derived from the liver cancer MHCC97 cell line through downregulation of β-catenin expression.
Consistent with its enrichment for CTNNB1 mutations (69%), lncRNA profile of the CTNNB1-enriched EEC subgroup was highly similar to that of the CTNNB1-enriched liver cancer subgroup.
Furthermore, using TOPflash and reverse transcription‑quantitative polymerase chain reaction analysis, Wnt/β‑catenin signaling and the transcriptional regulation of Wnt/β‑catenin target genes including dickkopf Wnt signaling pathway inhibitor 1, axis inhibition protein 2 and cyclin D1 were observed to be markedly upregulated in liver cancer SP cells.
Immunohistochemistry showed that all normal liver tissues and para-cancerous tissues examined showed membranous-type staining for beta-catenin protein, frequently with weak expression in the cytoplasm, but no beta-catenin accumulation in nuclei was found; while in liver cancer, 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei.
In conclusion, the EBP50/beta-catenin complex promotes Wnt signaling, and over-expression of EBP50 may work cooperatively with beta-catenin in the development of liver cancer.
In conclusion, we identified a number of candidate Wnt/beta-catenin target genes that can be useful for studying the role of altered Wnt signaling in liver cancer development, and showed that some of them might be direct targets of Wnt signaling in hepatoma cells.
Knockout of ASIC1a by CRISPR/CAS9 inhibited liver cancer cell proliferation and tumorigenicity in vitro and in vivo through β-catenin degradation and LEF-TCF inactivation.