Fig. 8. Platinum treatment stimulates autophagy in EOC cells.

WB analyses of p62, Cathepsin D (CTSD) and LC3I/LC3II expression in MDAH cells a or in control and SGK2-overexpressing OVCAR8 cells b treated with increasing doses of CBDCA for the indicated times. c WB analysis of autophagy markers in TOV21G cells overexpressing SGK2 WT, DN and KD mutants treated as in a and b for 16 h. GRB2 a or Vinculin b, c were used as loading control. d Schematic representation of the possible role of SGK2 role in the regulation of platinum sensitivity of EOC cells. Platinum treatment induces an autophagic response as a pro-survival pathway in which SGK2 acts as an autophagy stimulator. In SGK2 expressing cells, SGK2 by interacting with the lysosomal V-ATPase proton pump, ensures the maintenance of the correct acid pH necessary for the activation/maturation of lysosomal enzymes (left panel). Silencing or chemical inhibition of SGK2 results in V-ATPase disassembly, impaired lysosomal degradation capacity and the consequent inhibition of autophagic flux with accumulation of giant autophagolysosomes (depicted inside the cell, right panel). Autophagy inhibition eventually results in an increased EOC cells sensitivity to platinum treatment and enhanced cell death (right panel).