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Am J Physiol Cell Physiol 296: C221-C232, 2009. First published November 26, 2008; doi:10.1152/ajpcell.00514.2008
0363-6143/09 $8.00
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REVIEW

Muscarinic receptors and ligands in cancer

Nirish Shah, Sandeep Khurana, Kunrong Cheng, and Jean-Pierre Raufman

Division of Gastroenterology and Hepatology, VA Maryland Health Care System, Program in Oncology, Greenebaum Cancer Center, and Graduate Program in Life Sciences, University of Maryland School of Medicine, Baltimore, Maryland

Submitted 9 October 2008 ; accepted in final form 19 November 2008

ABSTRACT

Emerging evidence indicates that muscarinic receptors and ligands play key roles in regulating cellular proliferation and cancer progression. Both neuronal and nonneuronal acetylcholine production results in neurocrine, paracrine, and autocrine promotion of cell proliferation, apoptosis, migration, and other features critical for cancer cell survival and spread. The present review comprises a focused critical analysis of evidence supporting the role of muscarinic receptors and ligands in cancer. Criteria are proposed to validate the biological importance of muscarinic receptor expression, activation, and postreceptor signaling. Likewise, criteria are proposed to validate the role of nonneuronal acetylcholine production in cancer. Dissecting cellular mechanisms necessary for muscarinic receptor activation as well as those needed for acetylcholine production and release will identify multiple novel targets for cancer therapy.

tumor genesis; nonneuronal; cholinergic signaling; acetylcholine; bile acids


Address for reprint requests and other correspondence: J.-P. Raufman, Division of Gastroenterology and Hepatology, Univ. of Maryland School of Medicine, 22 South Greene St., N3W62, Baltimore, MD 21201 (e-mail: jraufman{at}medicine.umaryland.edu)






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