| Vitamin D inhibits CEACAM1 to promote insulin/IGF-I receptor signaling without compromising anti-proliferative action. | |
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MedLine Citation:
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PMID: 20714323 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Population studies suggest putative links between vitamin D (VD)-deficiency and risk of cancer and diabetes. The insulin/IGF-I receptor represents a signaling target of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) that is implicated in both diabetes and cancer, therefore we hypothesized that VD actions may be mediated through this adhesion molecule. In this study, we show that 1,25 vitamin D3 and its analogues EB1089 and KH1060 potently inhibit CEACAM1 expression in cancer cells. This effect was associated with significant reductions in mRNA and protein levels, resulting from transcriptional and posttranslational actions respectively. Insulin/IGF-I-mediated IRS-1 and Akt activation were enhanced by VD treatment. Similarly, CEACAM1 downregulation significantly upregulated the insulin and IGF-I receptors and mimicked the effect of VD-mediated enhanced insulin/IGF-I receptor signaling. Despite improved insulin/IGF-I signaling, the anti-proliferative actions of VD were preserved in the absence or presence of forced CEACAM1 expression. Forced CEACAM1, however, abrogated the anti-invasive actions of VD. Our findings highlight CEACAM1 as a target of VD action. The resulting inhibition of CEACAM1 has potentially beneficial effects on metabolic disorders without necessarily compromising the anticancer properties of this vitamin. |
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Authors:
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Wei Liu; Miao Guo; Shereen Ezzat; Sylvia L Asa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-16 |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: 91 ISSN: 1530-0307 ISO Abbreviation: Lab. Invest. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: United States |
Other Details:
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Languages: eng Pagination: 147-56 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Toronto, Toronto, Ontario, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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