Research ArticleCancer

Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis

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Science Signaling  20 Feb 2018:
Vol. 11, Issue 518, eaao0422
DOI: 10.1126/scisignal.aao0422

An Abl target in metastatic melanoma

Melanoma cells secrete proteases called cathepsins, which degrade the extracellular matrix and facilitate cell migration and invasion. Tripathi et al. found that cathepsin secretion was promoted by the nonreceptor tyrosine kinase Abl. Activation of Abl or a related kinase Arg promoted cathepsin B and cathepsin L expression and secretion by cell type–specific mechanisms involving transcription factors associated with the epithelial-mesenchymal transition and cancer progression. Analysis in a mouse model of metastatic melanoma suggested that Abl and Arg inhibitors may be a way to inhibit cathepsins and treat patients with metastatic melanoma.