Abstract
The mammalian target of rapamycin (mTOR) is an important signaling protein that integrates external and internal signals to regulate essential cell functions in a variety of organisms. Deregulation of the mTOR-dependent pathway occurs in many human diseases and may be a selective target for their therapy.
However, clinical results obtained by targeting this pathway with mTOR-specific inhibitor rapamycin have shown its limited therapeutic effects. We have found that mTOR signaling is highly upregulated in melanoma cells.
This hyperactivity could be reduced by treatment of the cells with rapamycin and by suppression of the activity of tyrosine kinase c-Src, which is comparable with the effect of rapamycin. Inhibition by the Src inhibitor does not lead to phosphorylation of Akt that can be induced by rapamycin, probably by a feedback machanism.