Figure 6.

Proposed model for the effects of hypoxia-induced energy stress on them TOR pathway in HNSCC cells. In response to ATP depletion associated with prolonged hypoxia, REDD1 plays a key role integrating yet to be elucidated signals that depend on the activation of the AMPK energy-sensing apparatus to promote mTOR substrate dephosphorylation in a TSC-dependent fashion. In addition, REDD1 acts as a critical negative regulator of mTOR activity in response to acute hypoxia independently on the cellular energy status.