The adenomatous polyposis coli (APC) protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer.
MIR100HG, miR-100 and miR-125b overexpression was also observed in cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell lines and in tumors from colorectal cancer patients that progressed on cetuximab. miR-100 and miR-125b coordinately repressed five Wnt/β-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness.
Aberrant regulation of the Wnt/β-catenin pathway has an important role during the onset and progression of colorectal cancer, with over 90% of cases of sporadic colon cancer featuring mutations in APC or β-catenin.
Finally, we observed for the first time that its expression negatively correlates with the activity of Wnt/β-catenin pathway, which is constitutively activated in colorectal cancer.
Notch is known to be a strong promoter of tumor initiation, but here we uncovered an unexpected suppressive role of Notch1 on WNT/β-catenin target genes involved in colorectal cancer.
Mutations in the APC or β-catenin genes are well-established initiators of colorectal cancer, yet modifiers that facilitate the survival and progression of nascent tumor cells are not well defined.
Human telomerase reverse transcriptase recruits the β-catenin/TCF-4 complex to transactivate chemokine (C-C motif) ligand 2 expression in colorectal cancer.
Postdiagnosis physical activity was associated with better colorectal cancer-specific survival only among patients with negative status for nuclear CTNNB1.
Given its ability to inhibit Wnt/β-catenin-mediated transcription in vitro and in vivo, as well as its efficacy in preclinical models of colorectal cancer and other Wnt-driven diseases, we examined ICG-001 and its potential role as a therapeutic in PDAC.
The MSI-positive tumors were screened for mutations in exon 3 of beta-catenin, which has been suggested to substitute for the APC mutation in the genesis of colorectal cancer, without finding mutations in any of the 22 MSI-positive tumors.
In the study reported here, we analyzed oncogenic beta-catenin activation on the basis of its nuclear accumulation (NA) and compared the results with those of mutational activation of K-ras in 74 patients with colorectal cancer to determine whether the two oncogene-mediated signaling cascades interact.
The mechanism of regulation of β-catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood.
Ad-CBR infection of colorectal cancer cell lines with mutant APC but wild-type beta-catenin resulted in substantial growth arrest followed by apoptosis.
We evaluated p53 and beta-catenin expressions in colorectal cancer specimens with known microsatellite status, previously assessed by means of the polymerase chain reaction (PCR).
We therefore suggest that AKT or β-catenin may potentially act as a therapeutic target to improve tumor regression and outcomes in colorectal cancer patients who harbored high-DDX3 tumors.