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

(2015) MOLECULAR & CELLULAR PROTEOMICS. 14(8). p.2213-2228
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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.
Keywords
COLORECTAL-CANCER, EMERGING ROLES, SHOTGUN PROTEOMICS, QUANTITATIVE PROTEOMICS, MULTISTAGE TUMORIGENESIS, TUMOR MICROENVIRONMENT, EPIDERMAL-GROWTH-FACTOR, GTPASE-ACTIVATING PROTEIN, BREAST-CANCER, CUTTING EDGE

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MLA
Sobotič, Barbara et al. “Proteomic Identification of Cysteine Cathepsin Substrates Shed from the Surface of Cancer Cells.” MOLECULAR & CELLULAR PROTEOMICS 14.8 (2015): 2213–2228. Print.
APA
Sobotič, B., Vizovišek, M., Vidmar, R., Van Damme, P., Gocheva, V., Joyce, J. A., Gevaert, K., et al. (2015). Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells. MOLECULAR & CELLULAR PROTEOMICS, 14(8), 2213–2228.
Chicago author-date
Sobotič, Barbara, Matej Vizovišek, Robert Vidmar, Petra Van Damme, Vasilena Gocheva, Johanna A Joyce, Kris Gevaert, Vito Turk, Boris Turk, and Marko Fonović. 2015. “Proteomic Identification of Cysteine Cathepsin Substrates Shed from the Surface of Cancer Cells.” Molecular & Cellular Proteomics 14 (8): 2213–2228.
Chicago author-date (all authors)
Sobotič, Barbara, Matej Vizovišek, Robert Vidmar, Petra Van Damme, Vasilena Gocheva, Johanna A Joyce, Kris Gevaert, Vito Turk, Boris Turk, and Marko Fonović. 2015. “Proteomic Identification of Cysteine Cathepsin Substrates Shed from the Surface of Cancer Cells.” Molecular & Cellular Proteomics 14 (8): 2213–2228.
Vancouver
1.
Sobotič B, Vizovišek M, Vidmar R, Van Damme P, Gocheva V, Joyce JA, et al. Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells. MOLECULAR & CELLULAR PROTEOMICS. 2015;14(8):2213–28.
IEEE
[1]
B. Sobotič et al., “Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells,” MOLECULAR & CELLULAR PROTEOMICS, vol. 14, no. 8, pp. 2213–2228, 2015.
@article{6981234,
  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.},
  author       = {Sobotič, Barbara and Vizovišek, Matej and Vidmar, Robert and Van Damme, Petra and Gocheva, Vasilena and Joyce, Johanna A and Gevaert, Kris and Turk, Vito and Turk, Boris and Fonović, Marko},
  issn         = {1535-9476},
  journal      = {MOLECULAR & CELLULAR PROTEOMICS},
  keywords     = {COLORECTAL-CANCER,EMERGING ROLES,SHOTGUN PROTEOMICS,QUANTITATIVE PROTEOMICS,MULTISTAGE TUMORIGENESIS,TUMOR MICROENVIRONMENT,EPIDERMAL-GROWTH-FACTOR,GTPASE-ACTIVATING PROTEIN,BREAST-CANCER,CUTTING EDGE},
  language     = {eng},
  number       = {8},
  pages        = {2213--2228},
  title        = {Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells},
  url          = {http://dx.doi.org/10.1074/mcp.M114.044628},
  volume       = {14},
  year         = {2015},
}

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