ß-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells.

ABSTRACT

BACKGROUND/AIMS: ß-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down ß-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between ß-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of ß-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. RESULTS: ß-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with ß-catenin and contributed to ß-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/ß-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and ß-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. CONCLUSIONS: Our study has provided new evidence for the role of ß-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of ß-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.