BEX2 regulates autophagy by inhibiting PIK3CA-p85 interaction in non-small-cell lung cancer cells.

BACKGROUND: Autophagy is an evolutionarily conserved cellular process that maintains homeostasis. It enables tumor cells to survive and grow, which may lead to drug resistance. The PI3K/AKT/mTOR pathway is reported to play a key role in autophagy induction. BEX2 promotes cell growth and survival in cancer cells. However, its role in autophagy remains unclear. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (A549, H1792 and H1299) and 293FT cells were used to investigate the function of BEX2 in autophagy. The experimental research was conducted via western blot, co-immunoprecipitation and confocal microscopy. RESULTS: Our data show that rapamycin induces BEX2 protein levels. Western blot and confocal microscopy analysis demonstrate that BEX2 regulates autophagy. Furthermore, BEX2 impairs PI3K/AKT/mTOR signaling. Specifically, BEX2 interacts with PIK3CA (PI3K catalytic subunit). BEX2 impairs the interaction of PIK3CA and p85 (PI3K regulatory subunit), therefore inhibiting PI3K activity. In summary, BEX2 regulates autophagy through the PI3K/AKT/mTOR signaling pathway by modulating the activity of PI3K, specifically dependent on the presence of PIK3CA. CONCLUSIONS: We discovered that BEX2 promotes autophagic flux via PI3K/AKT/mTOR signaling. BEX2 interacts with PIK3CA and impairs PIK3CA and p85 interaction, which hinders activation of PI3K/AKT/mTOR signaling and promotes autophagy induction.