SKP2 drives the sensitivity to neddylation inhibitors and cisplatin in malignant pleural mesothelioma.

ABSTRACT:

Background

The combination of pemetrexed and cisplatin remains the reference first-line systemic therapy for malignant pleural mesothelioma (MPM). Its activity is moderate because of tumor aggressiveness, immune-suppressive environment and resistance to chemotherapy-induced immunogenic cell death (ICD). Preliminary and limited findings suggest that MPM cells have deregulated ubiquitination and proteasome activities, although proteasome inhibitors achieved disappointing clinical results.

Methods

Here, we investigated the role of the E3-ubiquitin ligase SKP/Cullin/F-box (SCF) complex in cell cycle progression, endoplasmic reticulum (ER)/proteostatic stress and ICD in MPM, and the therapeutic potential of the neddylation/SCF complex inhibitor MLN4924/Pevonedistat.

Results

SUBMITTER: Salaroglio IC 

PROVIDER: S-EPMC8864928 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature