Nuclear immunoreactivities for beta -catenin and CTNNB1 mutations were restricted to independent uterine and ovarian tumors and were absent in all of the metastatic tumors, providing direct evidence for a divergence of molecular oncogenetic mechanisms in the subset of synchronous endometrioid carcinomas.
All children with beta-catenin nucleopositive large cell/anaplastic medulloblastomas and beta-catenin nucleopositive medulloblastomas presenting with metastatic disease are alive at least 5 years postdiagnosis.
The seven cases with nuclear accumulation of beta-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases.
Cyclin D1 staining was identified in 21 (59%) primary and 8 (80%) metastatic tumors, respectively, and nuclear beta-catenin in 24 (41%) primary and 7 (70%) metastatic tumors, respectively.
Cell lines with gain-of-function beta-catenin expressed up to 60-fold elevated S100A4 levels, displayed strongly increased migration and invasion in vitro, and induced metastasis in mice.
These results demonstrated that nm23-H1 can suppress the mobility and metastatic capacity of cancer cells and the molecular mechanism by which nm23-H1 suppresses tumor metastasis may be via increasing the expression of metastasis-related genes such as beta-Catenin, E-Cadherin and TIMP-1 and decreasing the expression of MMP-2, CD44V6 and VEGF.
To understand the molecular process of histogenesis of this tumor, a whole genome allelic imbalance (AI) scanning using a high-resolution single nucleotide polymorphism array as well as mutational analysis of the p53, EGFR, KRAS and beta-catenin genes were performed against the epithelial and mesenchymal components in the primary tumor and a metastatic tumor in a case of pulmonary blastoma.
The results of this study suggest an association between loss of expression of E-cadherin and beta-catenin and a lower degree of differentiation; however, their use as markers of nodal metastasis in OSCC appears unreliable.
Our results show that the class 2 gene expression signature was the most accurate predictor of metastasis (P=0.0001) and that the biomarkers most strongly associated with the class 2 signature included epithelioid cell type, beta-catenin, E-cadherin, and hypoxia-inducible factor 1alpha (P< or =0.001 for each).
Thirty-nine of the 113 cases were examined further for Dvl and beta-catenin protein expression in matched primary growths and autologous nodal metastases.
Although there was no significant association of protein levels with tumor invasion and metastasis, a significant correlation of nuclear SnoN and Ski with beta-catenin pathway was observed.
PIA treatment induced the expression of E-cadherin and beta-catenin, reduce that of Vimentin, restored their epithelial morphology of a polygonal shape, and reduced tumor cell migration in KB and KOSCC-25B cells, which was the corresponding feature of MErT.
Down-regulation of Wnt-5a expression and subsequent reduction of membrane-associated beta-catenin in invasive breast cancer, can therefore contribute to a decreased cell-cell adhesion and increased motility resulting in a higher probability for metastatic disease.
These actions involve direct physical interaction of TRbetaPV with cellular proteins, namely the regulatory subunit of the phosphatidylinositol 3-kinase (p85alpha), the pituitary tumor transforming gene (PTTG) and beta-catenin, that are critically involved in cell proliferation, motility, migration, and metastasis.
The L1 cell adhesion molecule (L1CAM) has been identified as a target gene of beta-catenin-TCF signaling in colorectal cancer (CRC) and associated with aggressive tumor behavior such as invasion and metastasis.
High CD24 expression was significantly associated with cytoplasmic and nuclear accumulation of beta-catenin (P = 0.023), high tumor proliferative status (P = 0.018), and diffused intrahepatic recurrence and distant metastasis (P = 0.026).