Macroautophagy/autophagy is an evolutionarily conserved intracellular process that recycles and degrades intracellular components to sustain homeostasis in response to deficiency of nutrients or
growth factors. PAQR3 is a newly discovered
tumor suppressor that also regulates autophagy induced by nutrient
starvation via AMPK and
MTORC1 signaling pathways. In this study, we investigated whether PAQR3 modulates EGFR-mediated autophagy and whether such regulation is associated with the
tumor suppressive activity of PAQR3. PAQR3 is able to inhibit the in vitro and in vivo growth of
non-small cell lung cancer (NSCLC) cells. PAQR3 potentiates autophagy induced by EGFR inhibitor
erlotinib. Knockdown of PAQR3 abrogates
erlotinib-mediated reduction of BECN1 interaction with autophagy inhibitory
proteins RUBCN/Rubicon and BCL2. PAQR3 blocks the interaction of BECN1 with the activated form of EGFR and inhibits
tyrosine phosphorylation of BECN1. Furthermore, inhibition of autophagy by knocking down ATG7 abrogates the
tumor suppressive activity of PAQR3 in NSCLC cells. Collectively, these data indicate that PAQR3 suppresses
tumor progression of NSCLC cells through modulating EGFR-regulated autophagy.
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