ALDH1A1 and HLTF modulate the activity of lysosomal autophagy inhibitors in cancer cells.

ABSTRACT: Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines. LAIs are being evaluated in cancer clinical trials, but genetic determinants of sensitivity to LAIs are unknown, making it difficult to predict which tumors would be most susceptible. Here we characterize differentially expressed genes in HCQ-sensitive (-S) and -resistant (-R) cancer cells. Notably, expression of canonical macroautophagy/autophagy genes was not associated with sensitivity to HCQ. Expression patterns of ALDH1A1 (aldehyde dehydrogenase 1 family member A1) and HLTF (helicase like transcription factor) identified HCQ-S (ALDH1A1_high HLTF_low; ALDH1A1_low HLTF_low) and HCQ-R (ALDH1A1_low HLTF_high

SUBMITTER: Piao S 

PROVIDER: S-EPMC5788553 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature