USP24 induces IL-6 in tumor-associated microenvironment by stabilizing p300 and ?-TrCP and promotes cancer malignancy.

ABSTRACT: We have previously demonstrated that USP24 is involved in cancer progression. Here, we found that USP24 expression is upregulated in M2 macrophages and lung cancer cells. Conditioned medium from USP24-knockdown M2 macrophages decreases the migratory and chemotactic activity of lung cancer cells and the angiogenic properties of human microvascular endothelial cell 1 (HMEC-1). IL-6 expression is significantly decreased in USP24-knockdown M2 macrophages and lung cancer cells, and IL-6-replenished conditioned medium restores the migratory, chemotactic and angiogenetic properties of the cells. USP24 stabilizes p300 and ?-TrCP to increase the levels of histone-3 acetylation and NF-?B, and decreases the levels of DNMT1 and I?B, thereby increasing IL-6 transcription in M2 macrophages and lung cancer cells, results in cancer malignancy finally. IL-6 has previously been a target for cancer drug development. Here, we provide direct evidence to support that USP24 promotes IL-6 expression, which might be beneficial for cancer therapy.

SUBMITTER: Wang YC 

PROVIDER: S-EPMC6162259 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature