Regulatory role of the α7nAChR in cancer.
Exposure to tobacco products is responsible for the majority of all human cancers. Nicotinic acetylcholine receptors (nAChRs) were identified as early as 1989 as important regulators of cancer cells. In analogy to its function in the brain, the homomeric α7nAChR has "accelerator function" on the most common human cancers by stimulating the synthesis and release of excitatory neurotransmitters (serotonin in small cell lung cancer, noradrenaline/adrenaline in most other cancers) that drive cell proliferation, migration, angiogenesis, neurogenesis and metastasis while inhibiting apoptosis. These effects are not only caused by α7nAChRs expressed in cancer cells but also by α7nAChRs in ganglia and nerves of the sympathetic part of the autonomic nervous system that release noradrenaline/adrenaline into the tumor environment. In the nervous system, α7nAChR protein undergoes paradoxical upregulation without concomitant desensitization upon chronic exposure to nicotine. The same phenomenon has been reported for α7nAChR expressed in cancer cells of the lungs and pancreas where chronic nicotine or nicotine-derived nitrosamines upregulated the receptor protein, resulting in hyperactivity of its effectors. Strategies that target the α7nAChR for cancer intervention are highly promising but should aim to reduce signaling downstream of the receptor rather than blocking the receptor because of its numerous vital functions in the mammalian organism.
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA. hmsch@utk.edu
Hildegard M
HM
Schuller
D000818:Animals; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced / Q000473:pathology*; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects; D064569:alpha7 Nicotinic Acetylcholine Receptor; D062789:Tobacco Products
C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine