Targeting USP8 inhibits Cancer Progression and Prevents EV-TβRII-Induced Exhaustion of CD8+ T cells

ABSTRACT: TGF-β signalling is a key player in tumor progression, immune evasion, and poor response to cancer immunotherapies. Here, we identified USP8 as a metastasis enhancer and a highly active deubiquitinase in aggressive breast tumors. USP8 acts as a cancer stemness-promoting factor that also mediates the activation of the TGF-β/SMAD signalling pathway. USP8 directly deubiquitinates and stabilises TβRII, increasing its expression in the plasma membrane and in tumor-derived extracellular vesicles (TEVs). Frequent gain of USP8 function was observed in patients resistant to neoadjuvant chemotherapies. USP8 promotes TGF-β/SMAD-induced epithelial to mesenchymal transition (EMT), invasion, and metastasis in tumor cells, and meanwhile, USP8 enables the TβRII+ circulating extracellular vesicles (crEVs)

SUBMITTER: Feng Xie 

PROVIDER: S-SCDT-EMBOJ-2021-108791 | biostudies-other |

REPOSITORIES: biostudies-other