Exosomes mediate intercellular transfer of non-autonomous tolerance to proteasome inhibitors in mixed-lineage leukemia.

ABSTRACT: Proteasome inhibitors significantly improve cancer outcomes, but their use is eventually followed by proteasome inhibitor resistance and relapse. Current understanding of proteasome inhibitor resistance is limited to cell-autonomous mechanisms; whether non-autonomous mechanisms can be implicated in the development of proteasome inhibitor resistance is unclear. Here, we show that proteasome inhibitor tolerance can be transmitted non-autonomously through exosome-mediated intercellular interactions. We revealed that reversible proteasome inhibitor resistance can be transmitted from cells under therapy stress to naïve sensitive cells through exosome-mediated cell cycle arrest and enhanced stemness in mixed-lineage leukemia cells. Integrated multi-omics analysis using the Tied Diffusion through

SUBMITTER: Ge M 

PROVIDER: S-EPMC7156829 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature