Focal adhesion kinase plays a dual role in TRAIL resistance and metastatic outgrowth of malignant melanoma.

ABSTRACT: Despite remarkable advances in therapeutic interventions, malignant melanoma (MM) remains a life-threating disease. Following high initial response rates to targeted kinase-inhibition metastases quickly acquire resistance and present with enhanced tumor progression and invasion, demanding alternative treatment options. We show 2^nd generation hexameric TRAIL-receptor-agonist IZI1551 (IZI) to effectively induce apoptosis in MM cells irrespective of the intrinsic BRAF/NRAS mutation status. Conditioning to the EC₅₀ dose of IZI converted the phenotype of IZI-sensitive parental MM cells into a fast proliferating and invasive, IZI-resistant metastasis. Mechanistically, we identified focal adhesion kinase (FAK) to play a dual role in phenotype-switching. In the cytosol, activ

SUBMITTER: Del Mistro G 

PROVIDER: S-EPMC8755828 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature