Oncotarget

Research Papers:

MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells

Ting Yang, Wanming He, Fei Cui, Jianling Xia, Rui Zhou, Zhenzhen Wu, Yang Zhao and Min Shi _

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Oncotarget. 2016; 7:18085-18094. https://doi.org/10.18632/oncotarget.7634

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Abstract

Ting Yang1,*, Wanming He1,*, Fei Cui1,*, Jianling Xia1, Rui Zhou1, Zhenzhen Wu1, Yang Zhao1 and Min Shi1

1 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Min Shi, email:

Keywords: acetylcholine, MACC1, gastric cancer, invasion, migration

Received: October 29, 2015 Accepted: February 11, 2016 Published: February 23, 2016

Abstract

The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1. These findings suggest that ACh acts via a M3R/AMPK/MACC1 signaling pathway to promote GC cell invasion/migration, which provides insight into the mechanisms underlying GC growth and metastasis and may shed light on new targets for GC treatment.


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