Muscarinic receptors and ligands in cancer.
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.
Shah
Nirish
N
Division of Gastroenterology and Hepatology, Univ. of Maryland School of Medicine, 22 South Greene St., N3W62, Baltimore, MD 21201, USA.
Khurana
Sandeep
S
Cheng
Kunrong
K
Raufman
Jean-Pierre
JP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D008024:Ligands; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D011487:Protein Conformation; D011976:Receptors, Muscarinic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D008024:Ligands; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine