Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors.
And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and β-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a.
The Wnt/beta-catenin signalling pathway is activated in 90% of human colon cancers by nuclear accumulation of beta-catenin protein due to its own mutation or to that of adenomatous polyposis coli.
Overall, the current study has identified activation of the Wnt/β-catenin pathway as a novel fundamental cause of colon cancer resistance to BRAF inhibition.
Immunohistochemical staining and western blotting experiments revealed that in colon cancer cells with SNHG1 knockdown, β-catenin, c-Myc and cyclin D1 protein levels were decreased, while E-cadherin was increased, which suggested that SNHG1 promoted colon cancer cell proliferation, migration and invasion through the Wnt/β-catenin signaling pathway.
In conclusion, targeting CBP/β-catenin, combined with PD-1/PD-L1 immune checkpoint blockade, shows potential as a new therapeutic strategy for treating liver metastasis during colon cancer.
Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating β-catenin and reducing the activation of β-catenin signaling.
Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/β-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/β-catenin signaling.
Mutation of the adenomatous polyposis coli and beta-catenin genes in colon cancer leads to constitutive activation of transcription from promoters containing binding sites for Tcf/LEF transcription factors.
In this study, we describe that truncated APC can still control the activity of beta-catenin in colon cancer cell lines via its first 20 amino acid repeat.
The transcriptional complex of β-catenin-T-cell factor (Tcf), a key mediator of canonical Wnt signaling, has been implicated in human colon cancer development.
The activity of beta-catenin, commonly dysregulated in human colon cancers, is inhibited by the vitamin D receptor (VDR), and this mechanism is postulated to explain the putative anti-cancer activity of vitamin D metabolites in the colon.
In 30 human cell lines derived from different origins, axin2 and hnkd were expressed only in human colon cancer cell lines that are known to have activating mutations in the Wnt/beta-catenin pathway.
An aberrant accumulation of β-catenin in intestinal epithelial cells is relevant to the development and progression of colon cancer and is thus a potential target for the development of therapeutics for this malignancy.
Colon cancer cells secrete and express high levels of β-catenin, which may stimulate autocrine signaling and further enhance activities of the canonical Wnt signaling pathway.