Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells Journal Article


Authors: Sobotič, B.; Vizovišek, M.; Vidmar, R.; Van Damme, P.; Gocheva, V.; Joyce, J. A.; Gevaert, K.; Turk, V.; Turk, B.; Fonović, M.
Article Title: 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 in extracellular shedding. In addition to influencing cell migration and invasion, shedding of surface proteins by extracellular cathepsins impacts intracellular signaling as demonstrated for regulation of Ras GTPase activity, thereby providing a putative mechanistic link between extracellular cathepsin activity and cancer progression. The MS data is available via ProteomeXchange with identifier PXD002192. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: unclassified drug; human cell; nonhuman; pancreas cancer; flow cytometry; mass spectrometry; animal cell; mouse; animal experiment; animal model; enzyme activity; proteomics; carcinogenesis; extracellular matrix; cancer cell; membrane protein; western blotting; ras protein; protein deficiency; cathepsin; macrophage; protein determination; coculture; cysteine cathepsin; cathepsin s; cysteine proteinase; human; priority journal; article; cancer cell line; cell migration assay
Journal Title: Molecular & Cellular Proteomics
Volume: 14
Issue: 8
ISSN: 1535-9476
Publisher: Amer Soc Biochemistry Molecular Biology Inc  
Date Published: 2015-08-01
Start Page: 2213
End Page: 2228
Language: English
DOI: 10.1074/mcp.M114.044628
PROVIDER: scopus
PMCID: PMC4528248
PUBMED: 26081835
DOI/URL:
Notes: Export Date: 2 September 2015 -- Source: Scopus
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MSK Authors
  1. Johanna A Joyce
    67 Joyce
  2. Vasilena Gocheva
    15 Gocheva