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. 2020 Feb 12;117(8):4158–4168. doi: 10.1073/pnas.1917938117

Fig. 6.

Fig. 6.

Defective macropinocytosis after pitavastatin induces protein and amino acid starvation in PTEN−/− cells. (A) The sensitivity of pitavastatin increases in PTEN−/− cells under serum-free conditions. (Scale bar, 30 μm.) (B) BSA rescues the cytotoxic effects of pitavastatin in mammalian PTEN−/− cells under serum-free conditions. (Scale bar, 30 μm.) (C) Total intracellular BSA in MCF10A and PTEN−/− cells increases with increasing concentrations of BSA in the medium (mean ± SD, n = 3). (D) Leucine (Leu) rescues the cytotoxic effects of pitavastatin on mammalian PTEN−/− cells under serum-free conditions. (Scale bar, 30 μm.) (E) Fluid-phase uptake in Dictyostelium pten cells in HL5 medium and FM medium. pten cells in HL5 medium were added with 1 μM pitavastatin; pten cells in FM medium were added with 4 μM pitavastatin. (Scale bar, 20 μm.) (F) Measurement of fluid-phase uptake in Dictyostelium pten cells in HL5 medium and FM medium (n = 3 experiments, nonparametric Mann–Whitney–Wilcoxon test, ****P < 0.0001). (G) Dictyostelium pten cells show resistance to pitavastatin in FM medium containing abundant amino acids. (Scale bar, 20 μm.) (H) Proposed molecular architecture of the mevalonate pathway and macropinocytosis.