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.