Quantitative proteomics links the intermediate filament nestin to resistance to targeted BRAF inhibition in melanoma cells.

Quantitative proteomics links the intermediate filament nestin to resistance to targeted BRAF inhibition in melanoma cells. Mol Cell Proteomics. 2019 Mar 19;: Authors: Schmitt M, Sinnberg T, Nalpas NC, Maass A, Schittek B, Macek B Abstract Targeted inhibition of mutated kinases using selective MAP kinase inhibitors in malignant melanoma often results in temporary improvement of clinical symptoms followed by rapid development of resistance. To gain insights in molecular processes that govern resistance, we performed SILAC-based quantitative proteomics profiling of vemurafenib-resistant and -sensitive melanoma cells. Among down-regulated proteins in vemurafenib-resistant cell lines we detected multiple proteins involved in cytoskeletal organization and signaling, including the intermediate filament nestin, which was one of the most down-regulated proteins. Previous studies showed that nestin is expressed in various types of solid tumors and its abundance correlates with malignant phenotype of transformed cells. However, the role of nestin in cancer cells with regard to acquired resistance is still poorly understood. We performed CRISPR/Cas9 knockout of the nestin gene (NES) in vemurafenib-sensitive cells and showed that loss of nestin leads to increased cellular proliferation and colony formation upon treatment with BRAFV600E and MEK inhibitors. Moreover, nestin depletion led to increased invasiveness and metalloproteinase activity sim...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research