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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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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)
- Urheber
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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
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
- 14.08.2025, 11:02 MESZ
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Beteiligte
- Grozdanić, Marija
- Sobotič, Barbara
- Biasizzo, Monika
- Sever, Tilen
- Vidmar, Robert
- Vizovišek, Matej
- Turk, Boris
- Fonović, Marko
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