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

β-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. We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of β-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. β-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 β-catenin and contributed to β-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/β-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. 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. Our study has provided new evidence for the role of β-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of β-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.

Yu W ，Li L ，Zheng F ，Yang W ，Zhao S ，Tian C ，Yin W ，Chen Y ，Guo W ，Zou L ，Deng W ... -  《-》

Inhibition of CREB binding protein-beta-catenin signaling down regulates CD133 expression and activates PP2A-PTEN signaling in tumor initiating liver cancer cells.

Tang Y ，Berlind J ，Mavila N 《Cell Communication and Signaling》

The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.

Wiese M ，Walther N ，Diederichs C ，Schill F ，Monecke S ，Salinas G ，Sturm D ，Pfister SM ，Dressel R ，Johnsen SA ，Kramm CM ... -  《Oncotarget》

Therapeutic targeting of CBP/β-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin.

Chan KC ，Chan LS ，Ip JC ，Lo C ，Yip TT ，Ngan RK ，Wong RN ，Lo KW ，Ng WT ，Lee AW ，Tsao GS ，Kahn M ，Lung ML ，Mak NK ... -  《Scientific Reports》

CREB-binding protein regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathway.

CBP (CREB-binding protein) is a transcriptional co-activator which possesses HAT (histone acetyltransferases) activity and participates in many biological processes, including embryonic development, growth control and homeostasis. However, its roles and the underlying mechanisms in the regulation of carcinogenesis and tumor development remain largely unknown. Here we investigated the molecular mechanisms and potential targets of CBP involved in tumor growth and survival in lung cancer cells. Elevated expression of CBP was detected in lung cancer cells and tumor tissues compared to the normal lung cells and tissues. Knockdown of CBP by siRNA or inhibition of its HAT activity using specific chemical inhibitor effectively suppressed cell proliferation, migration and colony formation and induced apoptosis in lung cancer cells by inhibiting MAPK and activating cytochrome C/caspase-dependent signaling pathways. Co-immunoprecipitation and immunofluorescence analyses revealed the co-localization and interaction between CBP and CPSF4 (cleavage and polyadenylation specific factor 4) proteins in lung cancer cells. Knockdown of CPSF4 inhibited hTERT transcription and cell growth induced by CBP, and vice versa, demonstrating the synergetic effect of CBP and CPSF4 in the regulation of lung cancer cell growth and survival. Moreover, we found that high expression of both CBP and CPSF4 predicted a poor prognosis in the patients with lung adenocarcinomas. Collectively, our results indicate that CBP regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathways.

Tang Z ，Yu W ，Zhang C ，Zhao S ，Yu Z ，Xiao X ，Tang R ，Xuan Y ，Yang W ，Hao J ，Xu T ，Zhang Q ，Huang W ，Deng W ，Guo W ... -  《-》