Cancers 2011, 3(1), 971-981; doi:10.3390/cancers3010971
Review

Muscarinic Receptor Signaling in Colon Cancer

1,2,* email and 1,2email
Received: 31 January 2011; in revised form: 14 February 2011 / Accepted: 24 February 2011 / Published: 2 March 2011
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Abstract: According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.
Keywords: colon cancer; bile acids; muscarinic receptors; epidermal growth factor receptors
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Von Rosenvinge, E.C.; Raufman, J.-P. Muscarinic Receptor Signaling in Colon Cancer. Cancers 2011, 3, 971-981.

AMA Style

Von Rosenvinge EC, Raufman J-P. Muscarinic Receptor Signaling in Colon Cancer. Cancers. 2011; 3(1):971-981.

Chicago/Turabian Style

Von Rosenvinge, Erik C.; Raufman, Jean-Pierre. 2011. "Muscarinic Receptor Signaling in Colon Cancer." Cancers 3, no. 1: 971-981.



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