Abstract:
Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent
losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide
3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway.
This study was designed to examine MYO1C expression status in a panel of wellstratified
endometrial carcinomas as well as to assess the biological significance of
MYO1C as a tumor suppressor in vitro. We found a significant correlation between the
tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell
transfection experiments, we found a negative correlation between MYO1C expression
and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion.
Cells expressing excess of MYO1C had low basal level of phosphorylated protein
kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a
quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken
together the present study gives further evidence for tumor suppressor activity of MYO1C
and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K
pathway and its involvement in loss of contact inhibition.
