Suppression of heparan sulfation re-sensitizes YAP1-driven melanoma to MAPK pathway inhibitors.

ABSTRACT: Accumulating evidence identifies non-genetic mechanisms substantially contributing to drug resistance in cancer patients. Preclinical and clinical data implicate the transcriptional co-activators YAP1 and its paralog TAZ in resistance to multiple targeted therapies, highlighting the strong need for therapeutic strategies overcoming YAP1/TAZ-mediated resistance across tumor entities. Here, we show particularly high YAP1/TAZ activity in MITF^low/AXL^high melanomas characterized by resistance to MAPK pathway inhibition and broad receptor tyrosine kinase activity. To uncover genetic dependencies of melanoma cells with high YAP1/TAZ activity, we used a genome-wide CRISPR/Cas9 functional screen and identified SLC35B2, the 3'-phosphoadenosine-5'-phosphosulfate transporter of t

SUBMITTER: Dieter SM 

PROVIDER: S-EPMC9355870 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature