ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology
Sorafenib is a multikinase inhibitor widely used in cancer therapy with an antitumoureffect related to biological processes as proliferation, migration or invasion, amongothers. Initially designed as a Raf inhibitor, Sorafenib was later shown to also block keymolecules in tumour progression such as...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2021 |
| Country: | España |
| Institution: | Universidad Autónoma de Madrid |
| Repository: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Language: | English |
| OAI Identifier: | oai:dnet:biblosearchi::01db6932f8d37be696bd1c03e94dcf16 |
| Online Access: | https://hdl.handle.net/10486/773000 https://dx.doi.org/10.1111/jcmm.16990 |
| Access Level: | Open access |
| Keyword: | EGF ERK5 MEK5 Sorafenib Biología y Biomedicina / Biología Química Medicina |
| Summary: | Sorafenib is a multikinase inhibitor widely used in cancer therapy with an antitumoureffect related to biological processes as proliferation, migration or invasion, amongothers. Initially designed as a Raf inhibitor, Sorafenib was later shown to also block keymolecules in tumour progression such as VEGFR and PDGFR. In addition, sorafenibhas been connected with key signalling pathways in cancer such as EGFR/EGF.However, no definitive clue about the molecular mechanism linking sorafenib andEGF signalling pathway has been established so far. Our data in HeLa, U2OS, A549and HEK293T cells, based on in silico, chemical and genetic approaches demonstratethat the MEK5/ERK5 signalling pathway is a novel target of sorafenib. In addition, ourdata show how sorafenib is able to block MEK5- dependent phosphorylation of ERK5in the Ser218/Tyr220, affecting the transcriptional activation associated with ERK5.Moreover, we demonstrate that some of the effects of this kinase inhibitor onto EGFbiological responses, such as progression through cell cycle or migration, are mediatedthrough the effect exerted onto ERK5 signalling pathway. Therefore, our observations describe a novel target of sorafenib, the ERK5 signalling pathway, and establish newmechanistic insights for the antitumour effect of this multikinase inhibitor |
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