IndraLab

"Professor Li and his team found that USP8 antagonized ferroptosis by stabilizing GPX4 in tumor cells and indicated that targeting USP8 may serve as a potential therapeutic strategy to promote ferroptosis to enhance cancer immunotherapy [96]."

"Immunohistochemistry (IHC) analysis of the expression of prostaglandin-endoperoxide synthase-2 (PTGS2), a marker for the assessment of oxidative stress and ferroptosis in vivo, indicated the combination effect of knocking down USP8 and erastin treatment in triggering tumor ferroptosis in vivo (Fig. 1L)."

"Targeting USP8 inhibits the proliferation of HCC and induces cell ferroptosis."

"To further confirm the role of ferritinophagy in USP8-mediated ferroptosis, we exploited two typical pharmacological inhibitors of autophagy: BAF and chloroquine (CQ) to block the autophagy."

"Moreover, we constructed SQSTM1 knockdown HepG2 cells as control, shSQSTM1 cells were resistant to elastin-induced ferroptosis, and knockdown of ATG7 or SQSTM1 greatly reduced the sensitivity of the shUSP8 MEF cells to erastin-induced ferroptosis and decreased lipid ROS level (Fig. 2C and 2D), while reconstituting SQSTM1 in shUSP8/shSQSTM1 MEF cells partially restored cellular ferroptosis sensitivity (Fig. 2D), indicating USP8-mediated ferroptosis is an autophagy-dependent process involving SQSTM1 participation.As two important marker proteins of ferritinophagy, nuclear receptor coactivator 4 (NCOA4) and FTL are always degraded under ferroptosis, which may be regulated by SQSTM1."