Drug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP.

ABSTRACT: The tumor suppressor DAB2IP, a RasGAP and cytoplasmic adaptor protein, modulates signal transduction in response to several extracellular stimuli, negatively regulating multiple oncogenic pathways. Accordingly, the loss of DAB2IP in tumor cells fosters metastasis and enhances chemo- and radioresistance. DAB2IP is rarely mutated in cancer but is frequently downregulated or inactivated by multiple mechanisms. Solid experimental evidence shows that DAB2IP reactivation reduces cancer aggressiveness in tumors driven by multiple different oncogenic mutations, making this protein an interesting target for cancer therapy. Considering this evidence, we screened a drug library to identify molecules that increase DAB2IP protein levels. We employed CRISPR/Cas9 gene editing to generate two prostate can

SUBMITTER: De Florian Fania R 

PROVIDER: S-EPMC12384208 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature