Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation.

ABSTRACT: Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca(2+) deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca(2+)-transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca(2+)] environments. BrdU pulse-labeling experiments suggest that low [Ca(2+)] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca(2+)] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein f

SUBMITTER: Dai W 

PROVIDER: S-EPMC3950320 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature