ALK inhibition activates LC3B-independent, protective autophagy in EML4-ALK positive lung cancer cells.

ABSTRACT: ALK inhibitors effectively target EML4-ALK positive non-small cell lung cancer, but their effects are hampered by treatment resistance. In the present study, we asked whether ALK inhibition affects autophagy, and whether this may influence treatment response. Whereas the impact of targeted therapies on autophagic activity previously have been assessed by surrogate marker proteins such as LC3B, we here thoroughly examined effects on functional autophagic activity, i.e. on the sequestration and degradation of autophagic cargo, in addition to autophagic markers. Interestingly, the ALK inhibitor Ceritinib decreased mTOR activity and increased GFP-WIPI1 dot formation in H3122 and H2228 EML4-ALK⁺ lung cancer cells, suggesting autophagy activation. Moreover, an mCherry-EGFP-LC3B based

SUBMITTER: Schlafli AM 

PROVIDER: S-EPMC8079437 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature