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Analysis of the acetylcholine‐signaling pathway reveals differences between normal and malignant lung tissue
Author(s) -
Brown Kathleen C,
Lau Jamie K,
Thornhill Brent A,
Perry Haley E,
Jones Dennie V,
Pulliam Joseph F,
Martin Jeremiah,
Dasgupta Piyali
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.699.4
Subject(s) - autocrine signalling , choline acetyltransferase , cancer research , acetylcholine , lung cancer , nicotine , medicine , vesicular acetylcholine transporter , signal transduction , acetylcholinesterase , cholinergic , receptor , biology , microbiology and biotechnology , enzyme , biochemistry
NSCLC is characterized by aggressive clinical course, rapid doubling time and a dismal survival rate. The development of NSCLC is closely correlated with smoking habits. A small percentage of NSCLC cases also occur in non‐smokers. Targeted therapies like EGFR‐inhibitors, EML‐ALK4 inhibitors, and B‐Raf inhibitors show excellent therapeutic response in NSCLC patients who are non‐smokers. However, they do not work well in NSCLC patients who are smokers. Therefore, the identification of novel molecular targets in NSCLC patients who are exposed to cigarette smoke is urgently needed. Tobacco components like nicotine and NNK have been known to accelerate the progression of lung cancer. One of the major mechanisms underlying the proliferative actions of nicotine and NNK is that they upregulate the levels of the growth factor acetylcholine (ACh). This ACh binds back to its target receptors (on NSCLC cells) and stimulates the proliferation of NSCLC cells in an autocrine manner. The ACh signaling loop is amplified by exposure to tobacco components and cigarette smoke. With this background in mind, we aim to compare the ACh‐signaling machinery between normal lung cells and NSCLC cells. We find that both normal lung epithelial cells and NSCLC cells express all the components of the ACh‐signaling pathway, namely choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and choline transporter (ChT). Some of the ACh‐signaling proteins like ChAT, VAChT and AChE show differences in expression and activity between normal lung tissue and NSCLC cells. We believe that such differences may form the basis of targeted therapies in NSCLC patients who are exposed to cigarette smoke. Support or Funding Information Funding for our study was supported by the an NIH R15‐AREA Grant (1R15HL113681‐01A1), ACTSI Grant from Marshall University, the Flight Attendant Medical Research Institute YCSA Grant (82115),and the West Virginia IDeA Network of Biomedical Research Excellence (P20RR016477 and P20GM103434).