Proteomic Identification of Cysteine Cathepsin Substrates Shed from the Surface of Cancer Cells.

ABSTRACT: Extracellular cysteine cathepsins are known to drive cancer progression, but besides degradation of extracellular matrix proteins little is known about their physiological substrates and thus the molecular mechanisms they deploy. One of the major mechanisms used by other extracellular proteases to facilitate cancer progression is proteolytic release of the extracellular domains of transmembrane proteins or ectodomain shedding. Here we show using a mass spectrometry-based approach that cathepsins L and S act as sheddases and cleave extracellular domains of CAM adhesion proteins and transmembrane receptors from the surface of cancer cells. In cathepsin S-deficient mouse pancreatic cancers, processing of these cathepsin substrates is highly reduced, pointing to an essential role of cathepsins

SUBMITTER: Sobotic B 

PROVIDER: S-EPMC4528248 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature