Muscarinic receptor M3 mediates cell proliferation induced by acetylcholine and contributes to apoptosis in gastric cancer.
The muscarinic receptor M3 is an acetylcholine receptor that regulates the activity of numerous fundamental central and peripheral nervous system functions. Recent studies have identified the activation of the M3 receptor in several cancers; however, the role of M3 in human gastric cancer (GC) remains largely unknown. In this study, we demonstrated that the M3 receptor was overexpressed in human GC tissues and was correlated with the cancer stage and with lymph node metastasis. In vitro, the M3 receptor enhanced the proliferation induced by acetylcholine in human GC cells, whereas the knockdown of M3 by a small hairpin RNA (shRNA) inhibited cell proliferation. Furthermore, M3 knockdown caused G2/M phase cell cycle arrest and induced apoptosis in human GC cells. In vivo, M3 knockdown suppressed tumorigenesis and promoted apoptosis in GC xenografts. In addition, we also detected the secretion of acetylcholine (ACh) by human GC cells and observed the co-expression of the M3 receptor and choline acetyltransferase (ChAT), the enzyme necessary for acetylcholine synthesis, in human GC tissues and cells. Taken together, our findings support an oncogenic role for the M3 receptor in gastric cancer, suggesting that M3 antagonists may serve as potential adjuvants to GC therapies. Further study of the underlying molecular mechanism could also lead to the identification of novel therapeutic targets for improved treatment of GC.
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Linjun
L
Wang
Department of General Surgery, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
Xiaofei
X
Zhi
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Qun
Q
Zhang
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Song
S
Wei
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Zheng
Z
Li
Department of Gastrointestinal Surgery, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People's Republic of China.
Jianping
J
Zhou
Department of Gastrointestinal Surgery, Taizhou People's Hospital, Taizhou, Jiangsu, 225500, People's Republic of China.
Jianguo
J
Jiang
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Yi
Y
Zhu
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Li
L
Yang
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
Hao
H
Xu
Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. xuzekuan@njmu.edu.cn.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. xuzekuan@njmu.edu.cn.
Zekuan
Z
Xu
D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
D043587:Receptor, Muscarinic M3; D000109:Acetylcholine
ACh; Apoptosis; Gastric cancer; M3; Proliferation