Inactivation of M2 AChR/NF-κB signaling axis reverses epithelial-mesenchymal transition (EMT) and suppresses migration and invasion in non-small cell lung cancer (NSCLC)

Oncotarget
Qingnan ZhaoLu Xu

Abstract

Non-neuronal cholinergic system is involved in lung physiology and lung cancer. However, the biochemical events downstream acetylcholine (ACh) receptor activation leading to carcinogenesis and tumor progression are not fully understood. Our previous work has shown that non-neuronal ACh acts as an autoparacrine growth factor to stimulate cell proliferation and promote epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) via activation of M2 muscarinic receptor (M2R). The aim of the present study was to delineate the underlying mechanisms linking M2R and lung tumor progression, which may provide potential therapeutic targets to delay lung cancer progression. Inhibition of M2R by antagonist or siRNA suppresses NSCLC cell migratory and invasive capacities, reverses EMT and simultaneously inactivates PI3K/Akt, MAPK ERK and NF-κB p65. On the other hand, M2R activation stimulates NSCLC migration and invasion and promotes EMT via NF-κB p65 activation. Moreover, NF-κB p65 activation induced by M2R activation was partially inhibited by either Akt or ERK inhibitor. Taken together, these results demonstrated for the first time that NF-κB p65 activation is essential in NSCLC progression associated with non-neuronal ...Continue Reading

References

Mar 12, 2003·Life Sciences·P SongE R Spindel
Oct 29, 2003·The Journal of Biological Chemistry·Bingbing JiangRichard A Cohen
Jan 18, 2005·Trends in Biochemical Sciences·Patrick ViatourAlain Chariot
Sep 22, 2005·Nature Reviews. Immunology·Michael Karin, Florian R Greten
Feb 7, 2008·Journal of Cellular Biochemistry·Chengyin MinGail E Sonenshein
Jun 19, 2008·Cancer Research·Pingfang SongEliot R Spindel
Oct 11, 2008·International Journal of Cancer. Journal International Du Cancer·Piyali DasguptaSrikumar Chellappan
Oct 21, 2009·PloS One·Rebecca DavisSrikumar Chellappan
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Canhui Guo, George R Stark
Jun 7, 2011·Biochemical Pharmacology·Ma Reina ImprogoPaul D Gardner
Jan 25, 2013·Nature Reviews. Cancer·Bram De Craene, Geert Berx
Apr 23, 2013·Oncogene·H Zheng, Y Kang
Oct 22, 2013·Genes & Development·Jeff H Tsai, Jing Yang
Dec 4, 2013·Pharmacology·Janet Beckmann, Katrin Susanne Lips
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
May 16, 2014·Nature Reviews. Cancer·Sergei A Grando

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Citations

Aug 10, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M Tibensky, B Mravec
Mar 24, 2018·Journal of Food and Drug Analysis·Chung-Chia LiaoChau-Jong Wang
Jun 18, 2021·Biological & Pharmaceutical Bulletin·Wenbing YingOuchen Wang
Jul 1, 2021·World Journal of Clinical Oncology·Alejandro EspañolMaría Elena Sales

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Methods Mentioned

BETA
nuclear translocation
scraping
light microscopy
transfection

Software Mentioned

Image J
GraphPad Prism
ImageJ

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