caa a22 4500 606237100 CHVBK 20210128101251.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s11010-014-2304-z doi (NATIONALLICENCE)springer-10.1007/s11010-014-2304-z Notch4 promotes gastric cancer growth through activation of Wnt1/β-catenin signaling [Elektronische Daten] [Cuijuan Qian, Fuqiang Liu, Bei Ye, Xin Zhang, Yong Liang, Jun Yao] Gastric cancer (GC) is one of the most common cancers and lethal malignancies in the world. Discovering novel biomarkers that correlate with GC may provide opportunities to reduce the severity of GC. As one of Notch receptor family members in mammals, Notch4 plays an important role in carcinogenesis of several tumors. However, the precise function and mechanism of Notch4 in GC remain undefined. To address this question, we investigated whether Notch4 could be involved in GC progression. We found that Notch4 was activated by overexpressing exogenous intracellular domain of Notch4 (ICN4), and Notch4 activation promoted GC growth in vitro and in vivo, while Notch4 inhibition using ICN4 siRNA had opposite effects. In addition, Notch4 activation induced expression and activation of Wnt1, β-catenin and downstream target genes, c-Myc and cyclin D1, in GC cells, while Notch4 inhibition had opposite effects. Moreover, β-catenin depletion by siRNA attenuated cell proliferation induced by Notch4 activation. Therefore, our results revealed that Notch4 activates Wnt1/β-catenin signaling to regulate GC growth. Springer Science+Business Media New York, 2014 Notch nationallicence Wnt1 nationallicence β-catenin nationallicence Gastric cancer nationallicence Growth nationallicence Qian Cuijuan Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut Liu Fuqiang Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut Ye Bei Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang Province, People's Republic of China aut Zhang Xin Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang Province, People's Republic of China aut Liang Yong Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut Yao Jun Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 165-174 0300-8177 401:1-2<165 2015 401 11010 https://doi.org/10.1007/s11010-014-2304-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2304-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Qian Cuijuan Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut NATIONALLICENCE 700 1- Liu Fuqiang Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut NATIONALLICENCE 700 1- Ye Bei Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang Province, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Xin Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang Province, People's Republic of China aut NATIONALLICENCE 700 1- Liang Yong Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut NATIONALLICENCE 700 1- Yao Jun Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 165-174 0300-8177 401:1-2<165 2015 401 11010