A majority of human colorectal tumors and hepatomas are known to possess a constitutively active canonical Wnt/beta-catenin/TCF signaling pathway, also express CR-1.
Aberrant activation of this signaling pathway is a key early event in the development of colorectal neoplasms, and is mainly caused by loss of function mutations in Adenomatous Polyposis Coli (APC), and less frequently by β-catenin stabilization mutations via missense or interstitial genomic deletions in CTNNB1.
Aberrant activation of Wnt signaling caused by mutations in adenomatous polyposis coli (APC) or beta-catenin is a critical event in the development of human colorectal tumors.
Aberrant activation of Wnt signaling caused by mutations in the tumor suppressor adenomatous polyposis coli or beta-catenin is a critical event in the development of human colorectal tumors.
Activator protein 2alpha associates with adenomatous polyposis coli/beta-catenin and Inhibits beta-catenin/T-cell factor transcriptional activity in colorectal cancer cells.
Alterations of phosphorylation sites within the CTNNB1 gene, which codes for beta-catenin has been reported to occur in about one-half of colorectal tumors without APC-gene mutations.
Because beta-catenin is constitutively active in the majority of colorectal tumors, it is unlikely that sFRP1 can act in the canonical Wnt response pathway.
Cell-cycle and apoptosis regulators (p16INK4A, p21CIP1, beta-catenin, survivin, and hTERT) and morphometry-defined MPECs predict metachronous cancer development in colorectal adenoma patients.
Collectively, our data indicate that KDM4B overexpression supports β-catenin mediated gene transcription and thereby contributes to the genesis of colorectal tumors.
Finally, we show that YAP expression is elevated in the majority of a panel of primary human colorectal tumors compared with its expression in uninvolved colonic mucosa, and that YAP and β-catenin localize to the nuclear compartment of tumor cells.
Increased triplex DNA-binding activity in vitro correlates with lymph node disease, metastasis, and reduced overall survival in colorectal cancer, and increased U2AF65 expression is associated with total and truncated beta-catenin expression in high-stage colorectal tumors.
Interestingly, the levels of Tbeta-4 mRNA, beta-catenin, c-Myc, and MMP-7 in metastatic liver lesions were relatively higher, whereas the levels of E-cadherin and Fas were significantly lower than those in the matched primary colorectal tumors.