caa a22 4500 606235485 CHVBK 20210128101242.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2477-0 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2477-0 Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells [Elektronische Daten] [Yan-Jie Lu, Zhi-Jun Geng, Xiao-Yan Sun, Yu-Hong Li, Xiao-Bing Fu, Xiang-Yang Zhao, Bo Wei] The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the β2-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that β2-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as α-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and β-catenin. Isoprenaline stimulation of β2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting β2-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression. Springer Science+Business Media New York, 2015 Gastric cancer nationallicence Stress nationallicence Epithelial-mesenchymal transition nationallicence Cancer stem cells nationallicence Lu Yan-Jie Department of General Surgery, Chinese PLA General Hospital, 28 Fu Xing Road, 100853, Beijing, People's Republic of China aut Geng Zhi-Jun Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of skin injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, 100048, Beijing, People's Republic of China aut Sun Xiao-Yan Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital, 100853, Beijing, People's Republic of China aut Li Yu-Hong Department of Pathology, Cancer Research Laboratory, Chengde Medical College, 067000, Chengde, Hebei, People's Republic of China aut Fu Xiao-Bing Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of skin injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, 100048, Beijing, People's Republic of China aut Zhao Xiang-Yang Department of General Surgery, The 266th hospital of Chinese PLA, 067000, Chengde, Hebei, People's Republic of China aut Wei Bo Department of General Surgery, Chinese PLA General Hospital, 28 Fu Xing Road, 100853, Beijing, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 1-13 0300-8177 408:1-2<1 2015 408 11010 https://doi.org/10.1007/s11010-015-2477-0 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/s11010-015-2477-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lu Yan-Jie Department of General Surgery, Chinese PLA General Hospital, 28 Fu Xing Road, 100853, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Geng Zhi-Jun Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of skin injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, 100048, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Sun Xiao-Yan Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital, 100853, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Li Yu-Hong Department of Pathology, Cancer Research Laboratory, Chengde Medical College, 067000, Chengde, Hebei, People's Republic of China aut NATIONALLICENCE 700 1- Fu Xiao-Bing Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of skin injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, 100048, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhao Xiang-Yang Department of General Surgery, The 266th hospital of Chinese PLA, 067000, Chengde, Hebei, People's Republic of China aut NATIONALLICENCE 700 1- Wei Bo Department of General Surgery, Chinese PLA General Hospital, 28 Fu Xing Road, 100853, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 1-13 0300-8177 408:1-2<1 2015 408 11010