PDF file - 117K, Supplementary table 1. Changes in shRNAs included in the autophagy library per cell line. Cells were transduced with a shRNA library containing autophagy-focused shRNAs. After transduction, the first sample (Post-transduction, PT) was collected. Growth sample (G) was collected after 15 days in culture. Both samples were done in quintuplicate. Table shows comparison of PT versus G samples. shRNAs were considered to be up (Sign Tag = U), or down-regulated (Sign Tag = D) in the growth sample when ANOVA p-value < 0.05 and fold change absolute value > 2.
ARTICLE ABSTRACT
Autophagy is a protein and organelle degradation pathway that is involved in diverse diseases, including cancer. Recent evidence suggests that autophagy is a cell survival mechanism in tumor cells and that its inhibition, especially in combination with other therapy, could be beneficial but it remains unclear if all cancer cells behave the same way when autophagy is inhibited. We inhibited autophagy in a panel of breast cancer cell lines and found that some of them are dependent on autophagy for survival even in nutrient rich conditions without any additional stress, whereas others need autophagy only when stressed. Survival under unstressed conditions is due to cell type–specific autophagy regulation of STAT3 activity and this phenotype is enriched in triple-negative cell lines. This autophagy-dependency affects response to therapy because autophagy inhibition reduced tumor growth in vivo in autophagy-dependent but not in autophagy-independent breast tumors, whereas combination treatment with autophagy inhibitors and other agent was preferentially synergistic in autophagy-dependent cells. These results imply that autophagy-dependence represents a tumor cell–specific characteristic where autophagy inhibition will be more effective. Moreover, our results suggest that autophagy inhibition might be a potential therapeutic strategy for triple-negative breast cancers, which currently lack an effective targeted treatment. Cancer Res; 74(9); 2579–90. ©2014 AACR.
