Cathepsin L-mediated EGFR cleavage affects intracellular signalling pathways in cancer
Abstract: Proteolytic activity in the tumour microenvironment is an important factor in cancer development since it can also affect intracellular signalling pathways via positive feedback loops that result in either increased tumour growth or resistance to anticancer mechanisms. In this study, we demonstrated extracellular cathepsin L-mediated cleavage of epidermal growth factor receptor (EGFR) and identified the cleavage site in the extracellular domain after R224. To further evaluate the relevance of this cleavage, we cloned and expressed a truncated version of EGFR, starting at G225, in HeLa cells. We confirmed the constitutive activation of the truncated protein in the absence of ligand binding and determined possible changes in intracellular signalling. Furthermore, we determined the effect of truncated EGFR protein expression on HeLa cell viability and response to the EGFR inhibitors, tyrosine kinase inhibitor (TKI) erlotinib and monoclonal antibody (mAb) cetuximab. Our data reveal the nuclear localization and phosphorylation of EGFR and signal trancducer and activator of transcription 3 (STAT3) in cells that express the truncated EGFR protein and suggest that these phenomena cause resistance to EGFR inhibitors.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Cathepsin L-mediated EGFR cleavage affects intracellular signalling pathways in cancer ; volume:405 ; number:4 ; year:2024 ; pages:283-296 ; extent:14
Biological chemistry ; 405, Heft 4 (2024), 283-296 (gesamt 14)
- Creator
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Grozdanić, Marija
Sobotič, Barbara
Biasizzo, Monika
Sever, Tilen
Vidmar, Robert
Vizovišek, Matej
Turk, Boris
Fonović, Marko
- DOI
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10.1515/hsz-2023-0213
- URN
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urn:nbn:de:101:1-2024032914404876261071
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 11:02 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Grozdanić, Marija
- Sobotič, Barbara
- Biasizzo, Monika
- Sever, Tilen
- Vidmar, Robert
- Vizovišek, Matej
- Turk, Boris
- Fonović, Marko
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Cathepsin B cleavage of the trypsinogen activation peptide
Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate
Novel fluorescent sensors for dynamic intracellular signalling
Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice
Molecular changes in EGFR downstream signalling and intracellular calcium changes associated with the cisplatin-resistant phenotype of lung cancer cells
Cleavage of Nidogen-1 by Cathepsin S Impairs Its Binding to Basement Membrane Partners
A pathway sensor for genome-wide screens of intracellular proteolytic cleavage
Lung macrophages utilize unique cathepsin K–dependent phagosomal machinery to degrade intracellular collagen
Cathepsin protease controls copper and Cisplatin accumulation via cleavage of the Ctr1 metal-binding ectodomain
Asparaginyl endopeptidase (legumain) supports human Th1 induction via cathepsin L-mediated intracellular C3 activation
The exosome journey: from biogenesis to uptake and intracellular signalling
Indirect inference of synergistic and alternative signalling of intracellular pathways
Cathepsin B cleavage of the trypsinogen activation peptide
Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate
Novel fluorescent sensors for dynamic intracellular signalling
Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice
Molecular changes in EGFR downstream signalling and intracellular calcium changes associated with the cisplatin-resistant phenotype of lung cancer cells
Cleavage of Nidogen-1 by Cathepsin S Impairs Its Binding to Basement Membrane Partners
A pathway sensor for genome-wide screens of intracellular proteolytic cleavage
Lung macrophages utilize unique cathepsin K–dependent phagosomal machinery to degrade intracellular collagen
Cathepsin protease controls copper and Cisplatin accumulation via cleavage of the Ctr1 metal-binding ectodomain
Asparaginyl endopeptidase (legumain) supports human Th1 induction via cathepsin L-mediated intracellular C3 activation
The exosome journey: from biogenesis to uptake and intracellular signalling