The integrin α6β4 activates Src to inhibit ferroptosis. (A) Vector control and β4-depleted cells were assessed for phosphorylated (Y418) Src by immunoblotting 3 h after ECM detachment. Relative phosphorylated Src was quantified by densitometry. (B) Vector control and β4-depleted cells were assessed for viability after 24 h of detachment in the presence of either DMSO, 10 µM PP2, PP2 and 2 µM ferrostatin-1, PP2 and 500 µM α-tocopherol, or PP2 and 2 µM liproxstatin-1. (C) Vector control and β4-depleted cells were assessed for phosphorylated (Y418) Src by immunoblotting after 3 h of incubation with 10 µM erastin. Relative phosphorylated Src was quantified by densitometry. (D) SUM-159 vector control and β4-depleted cells that expressed a doxycycline-inducible, constitutively active Src were incubated for 24 h with 2 µg/ml doxycycline and then assessed for viability after 24 h of detachment. All experiments were performed independently three times, and a representative experiment is shown. The bars in graphs represent means ± SD. *, P < 0.05; **, P < 0.01; ***, P < 0.005.