Blocking M2 muscarinic receptor signaling inhibits tumor growth and reverses epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC)

Cancer Biology & Therapy
Qingnan ZhaoLu Xu

Abstract

Lung cancers express non-neuronal, cholinergic autoparacrine loop, which facilitates tumor growth. Interruption of M3 muscarinic cholinergic signaling has been reported to inhibit small cell lung cancer (SCLC) growth. The purpose of this study is to investigate if blocking autoparacrine muscarinic cholinergic signaling could inhibit non-small cell lung cancer (NSCLC) growth and possible underlying mechanisms. Our results showed that PC9 and A549 cells expressed all 5 subtypes of muscarinic receptor (mAChR) and blocking M2 mAChR (M2R) signaling using selective antagonist methoctramine or short hairpin RNA (shRNA) inhibited tumor cell proliferation in vitro and in vivo. Consistent with AChR agonists stimulating p44/42 MAPK (Erk1/2) and Akt phosphorylation, blocking M2R signaling decreased MAPK and Akt phosphorylation, indicating that non-neuronal ACh functions as an autoparacrine growth factor signaling in part through activation of M2R and downstream MAPK and Akt pathways. Importantly, further studies revealed that blocking M2R signaling also reversed epithelial-mesenchymal transition (EMT) in vitro and in vivo, indicating that non-neuronal ACh promotes EMT partially through activation of M2R. These findings demonstrate that M2R...Continue Reading

References

Mar 1, 1979·Anesthesia and Analgesia·P KaniarisE Dermitzakis
Sep 1, 1988·Naunyn-Schmiedeberg's Archives of Pharmacology·J WessG Lambrecht
Jul 1, 1993·The Journal of Investigative Dermatology·S A GrandoM V Dahl
Apr 1, 1997·Naunyn-Schmiedeberg's Archives of Pharmacology·H KlapprothI Wessler
Dec 24, 1997·Naunyn-Schmiedeberg's Archives of Pharmacology·I WesslerR Hammer
Jul 7, 2000·Histochemistry and Cell Biology·R V HaberbergerW Kummer
Jun 21, 2002·Trends in Cell Biology·Philip J S Stork, John M Schmitt
Mar 12, 2003·Life Sciences·P SongE R Spindel
May 3, 2003·Pharmacology & Therapeutics·Chris J van Koppen, Björn Kaiser
Nov 8, 2005·Carcinogenesis·Pedro Martínez-MorenoJuan Cabezas-Herrera
May 2, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rong-Jane ChenYing-Jan Wang
May 27, 2008·British Journal of Pharmacology·I Wessler, C J Kirkpatrick
Jun 19, 2008·Cancer Research·Pingfang SongEliot R Spindel
Jul 26, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kunrong ChengJean-Pierre Raufman
Oct 11, 2008·International Journal of Cancer. Journal International Du Cancer·Piyali DasguptaSrikumar Chellappan
Nov 28, 2008·American Journal of Physiology. Cell Physiology·Nirish ShahJean-Pierre Raufman
Oct 21, 2009·PloS One·Rebecca DavisSrikumar Chellappan
Dec 4, 2013·Pharmacology·Janet Beckmann, Katrin Susanne Lips

❮ Previous
Next ❯

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
Apr 29, 2016·Biomedical Reports·Ningning DangHaiyan Song
May 3, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sandra Cristea, Julien Sage
Nov 14, 2020·International Journal of Molecular Sciences·Anna Maria LucianòAda Maria Tata
May 22, 2021·The Journal of International Medical Research·Meimei HeBinglong Bai
May 25, 2021·The Journal of Investigative Dermatology·Chandan K Sen, Sashwati Roy

❮ Previous
Next ❯

Methods Mentioned

BETA
Confocal microscopy
xenograft
xenografts
PCR

Software Mentioned

Image J
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.