Mechanical stress shapes the cancer cell response to neddylation inhibition.

ABSTRACT:

Background

The inhibition of neddylation by the preclinical drug MLN4924 represents a new strategy to combat cancer. However, despite being effective against hematologic malignancies, its success in solid tumors, where cell-cell and cell-ECM interactions play essential roles, remains elusive.

Methods

Here, we studied the effects of MLN4924 on cell growth, migration and invasion in cultured prostate cancer cells and in disease-relevant prostate tumoroids. Using focused protein profiling, drug and RNAi screening, we analyzed cellular pathways activated by neddylation inhibition.

Results

We show that mechanical stress induced by MLN4924 in prostate cancer cells significantly affects the therapeutic outcome. The latter depends on the cell type and involves distinct Rho is

SUBMITTER: Mittler F 

PROVIDER: S-EPMC8966269 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature