Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and β-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients.
Finally, bioinformatics analyses directed to identify which gene combinations had synergistic effects on clinical outcome in lung cancer showed that poor survival is associated with high co-expression of SCD1, β-catenin and the YAP/TAZ downstream target birc5.
In terms of clinical application, our definition of a five-gene CSC signature (nuclear β-catenin(High)/nuclear Twist1(High)/E-cadherin(Low)/Sox15(Low)/CD133(High)) may provide a useful prognostic marker for human lung cancer.
These data suggest that β-catenin plays an essential role in lung tumorigenesis and that targeting the β-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs.
LKB1 status influences the molecular circuitry (Wnt/β-catenin pathway), cellular biology, and may serve as a potential therapeutic node in genetically defined subsets of lung cancer.
Gao and collaborators (Tumour Biol, 2013) have investigated the role of mucin 4 (MUC4) in lung cancer and have concluded that a loss of MUC4 results in epithelial mesenchymal transition via beta-catenin nuclear translocation and that MUC4 expression is correlated with a risk of lymph node metastasis in a cohort of 20 lung adenocarcinoma patients.
Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.
In the current study, we expanded our analysis for the methylation status of β-catenin promoter region and its protein expression in seven NSCLC cell lines and a series of 143 cases of primary human lung cancer with adjacent non-neoplastic tissues.
TC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors.
Overall, the data show that airway basal cell β-catenin determines cell fate and its mis-expression is associated with the development of human lung cancer.
Overexpression of frequently rearranged in advanced T-cell lymphomas 1 (Frat1) has been reported in several human malignant tumors, but the relationship between Frat1 and β-catenin in lung cancer is still unclear.
In this study, using both novel and established technologies, we developed a clinically practical assay to survey the status of three frequently mutated genes in lung cancer (EGFR, K-ras and TP53) and two genes (BRAF and β-catenin) with known hotspot mutations in many other cancers.
Moreover, the data confirm a crucial role of CTNNB1 mutations in the pathogenesis of PB, and indicate that CTNNB1 gene sequencing may be a useful in distinguishing PB from other types of lung cancer.