Figure 6.

A model depicting a novel mechanism by which cetuximab induces autophagy. Activation of EGFR/class I PI3K/Akt/mTOR signaling pathway by EGF suppresses autophagy whereas inhibition of the pathway by cetuximab induces autophagy. Cetuximab downregulates HIF-1α, and subsequently decreases Bcl-2, which releases beclin 1 from its association with Bcl-2 to form complex with class III PI3K/hVps34 (directed with a dashed line); the latter complex thereby promotes autophagy. The arrow lines indicate the direction of pathways. The ⊥ symbolizes an inhibitory function by an agent or a molecule. The question mark implies additional mechanisms not explored in current study, by which HIF-1α may suppress autophagy.