These results suggest that tyrosine phosphorylation of beta-catenin regulated by c-erbB-2 protein may play an important role in the invasion, metastasis and morphogenesis of cancer cells and that inhibition of the aberrant tyrosine phosphorylation of beta-catenin effectively prevents invasion and metastasis of cancer cells.
To show the mRNA expressions of E-cadherin and alpha- and beta-catenin-which mainly compose the adherens junction-associated with invasion and metastasis of uterine cervical cancers, we studied the expression of E-cadherin and alpha- and beta-catenin mRNAs in cancers in comparison with normal counterparts.
Nuclear beta-catenin was found in dedifferentiated mesenchyme-like tumor cells at the invasive front, but strikingly, as in central areas of the primary tumors, was localized to the membrane and cytoplasm in polarized epithelial tumor cells in the metastases.
In our study, 43 primary cutaneous melanoma and 30 metastases were screened for CTNNB1 exon 3 mutations by using a denaturing gradient gel electrophoresis technique and sequencing. beta-Catenin mutations were found in 2 primary melanomas and 1 metastatic melanoma and were not correlated with nuclear accumulation of beta-catenin in these cases.
Analysis of primary human adenocarcinomas revealed that this MUC1/beta-catenin interaction occurs in both primary and metastatic tumors, but is dramatically increased in metastatic lesions.
To determine the role of beta-catenin in solid and cystic tumor (SCT) of the pancreas, a rare neoplasm usually observed in young females, we examined three primary tumors and one corresponding liver metastatic tumor presented in pediatric patients.
In conclusion, LOH and P53 protein overexpression, rather than mutations in the p53 or beta-catenin genes or MSI, seem to be involved in the spreading of HCC, suggesting the presence of metastasis suppressor genes in the vicinity of the chromosomal loci in question.
Immunohistochemistry and Western blot analysis were used to analyze the expression of beta-catenin in 87 human gastric cancers, in metastasis and cancer cell lines.
Importantly, most (7 of 8) patients with tumor showing both K-ras activation and the NAinv pattern of beta-catenin activation were in Dukes' stage C at surgery, and half of them developed distant metastases to the liver and lungs.
In five resected cases of pulmonary metastasis, translocation of beta-catenin to the cytoplasm and/or nucleus of osteosarcoma cells was detected, although seven primary osteosarcomas cells that did not metastasize for more than five years did not showbeta-catenin expression.
The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05).
Therefore, beta-catenin might have an impact on the capacity of colorectal tumors for invasion and metastasis, as well as dormancy, which are hallmarks of cancer.
Because beta-catenin and its target genes urokinase-type plasminogen activator receptor (uPAR) and cyclin D1 are overexpressed in colon cancers, and are linked to cancer growth, invasion, and metastasis, we investigated whether DCA activates beta-catenin signaling and promotes colon cancer cell growth and invasiveness.
In colorectal cancer, increased expression of beta-TrCP1 is associated with activation of both beta-catenin and NF-kappaB, suggesting that the integration of these signaling pathways by increased beta-TrCP expression may contribute to an inhibition of apoptosis and tumor metastasis.
However, altered expression of beta-catenin and E-cadherin correlated with metastatic disease, and these markers may have prognostic importance in rectal cancer.
Involvement of epigenetic and genetic aberrations in APC and beta-catenin genes seems to be of minor importance for the development of local recurrences and distant metastases.
Reduced expression of E-cadherin was found to be correlated with lymph node metastatic tumor of NPC (P = 0.004); but there was no obvious correlation between primary and metastatic tumors in the expression of beta-catenin (P = 0.698).
These observations suggest that the Wnt/beta-catenin signal transduction pathway is involved much more commonly in the molecular pathogenesis of HCC than previously recognized because FZD7 overexpression occurred early in the disease process, stabilized wild-type beta-catenin levels, and contributed to enhanced tumor cell migration.
Aberrant beta-catenin-TCF target gene activation plays a key role in colorectal cancer, both in the initiation stage and during invasion and metastasis.
The molecular mechanisms underlying the antagonistic regulation of beta-catenin-reptin and the Tip60 coactivator complexes for the metastasis suppressor gene, KAI1, are likely to be prototypic of a selective downregulation strategy for many genes, including a subset of NF-kappaB target genes.