Figure 9. Model for the mechanism of SOCS1 action in inhibition of EMT signaling through ROS suppression involving Src-mediated thioredoxin regulation in colon cancer cells.

In HCT116 cells, intracellular ROS generated upon exogenous hydrogen peroxide treatment stimulates Src and Jak kinase activation leading to p65 activation and modulation of EMT regulators such as up-regulation of vimentin and Snail accompanied with down-regulation of E-Cadherin. SOCS1 induced by ROS signal suppresses Src activity involving molecular interaction. The pY-Src activity is responsible for attenuation of nuclear Nrf-2 (nNrf-2) and thioredoxin (Trx) levels. Src inhibition by SOCS1, thus results in increased Trx and decreased ROS levels in SOCS1-transduced cells. Src inactivation leads to the reduced EMT signaling and invasion property. Jak inhibition during this process can be achieved directly by SOCS1 and via suppression of Src by SOCS1.