TY - JOUR T1 - Non cell-autonomous effects of autophagy inhibition in tumor cells promote growth of drug-resistant cells. JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.116.106070 SP - mol.116.106070 AU - Jacqueline Thorburn AU - Leah Staskiewicz AU - Megan L Goodall AU - Lina Dimberg AU - Arthur E Frankel AU - Heide L Ford AU - Andrew Thorburn Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/11/09/mol.116.106070.abstract N2 - Autophagy, the mechanism by which cells deliver material to the lysosome, has been associated with resistance to anti-cancer drugs, leading autophagy inhibition to be widely studied as a potential chemosensitization strategy for cancer cells. This strategy is based on the idea that inhibition of autophagy will increase drug sensitivity and kill more cancer cells. Here we report an unintended negative effect of this strategy. When modeling the effect of drug resistance in a heterogeneous cancer cell population, we found that autophagy inhibition in drug sensitive tumor cells causes increased growth of drug resistant cells in the population through a mechanism involving caspase activation and prostaglandin E2 signaling. These results emphasize the importance of understanding how autophagy manipulation in a tumor cell can have both cell-autonomous and non-autonomous effects, and suggest that attempts to chemosensitize by inhibiting autophagy could be enhanced by adopting methods aimed at reducing tumor repopulation. ER -