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Targeting the Src N-terminal regulatory element in cancer

The signaling pathways displayed by cancer cells are often composed by the same components than the physiological ones, yet the overall result is a pathological deregulation. The non-receptor protein tyrosine kinase Src is a good example. Src is the first described proto-oncogene and a demonstrated...

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Autores principales: Mezquita, Betlem, Reyes-Farias, Marjorie, Pons, Miquel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197966/
https://www.ncbi.nlm.nih.gov/pubmed/37204272
http://dx.doi.org/10.18632/oncotarget.28434
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author Mezquita, Betlem
Reyes-Farias, Marjorie
Pons, Miquel
author_facet Mezquita, Betlem
Reyes-Farias, Marjorie
Pons, Miquel
author_sort Mezquita, Betlem
collection PubMed
description The signaling pathways displayed by cancer cells are often composed by the same components than the physiological ones, yet the overall result is a pathological deregulation. The non-receptor protein tyrosine kinase Src is a good example. Src is the first described proto-oncogene and a demonstrated player in cancer progression, as it affects proliferation, invasion, survival, cancer stemness, and drug resistance. Src activation is linked to poor prognosis in many cancer types, yet mutations in this protein are rarely observed. In addition, being a demonstrated cancer target, unspecific inhibition of the kinase activity has proven inefficient in clinics since the inhibition of Src in non-cancerous cells results in unacceptable toxicity. Thus, there is a need for new target regions in Src that could inhibit Src activity only in certain cell types, e.g., cancer cells, while maintaining the normal physiological activity in healthy cells. The Src N-terminal regulatory element (SNRE) includes the poorly studied intrinsically disordered region with unique sequences for each of the members of the Src family. In this perspective, we discuss the non-canonical regulatory mechanisms involving the SNRE and their potential use as oncotargets.
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spelling pubmed-101979662023-05-20 Targeting the Src N-terminal regulatory element in cancer Mezquita, Betlem Reyes-Farias, Marjorie Pons, Miquel Oncotarget Research Perspective The signaling pathways displayed by cancer cells are often composed by the same components than the physiological ones, yet the overall result is a pathological deregulation. The non-receptor protein tyrosine kinase Src is a good example. Src is the first described proto-oncogene and a demonstrated player in cancer progression, as it affects proliferation, invasion, survival, cancer stemness, and drug resistance. Src activation is linked to poor prognosis in many cancer types, yet mutations in this protein are rarely observed. In addition, being a demonstrated cancer target, unspecific inhibition of the kinase activity has proven inefficient in clinics since the inhibition of Src in non-cancerous cells results in unacceptable toxicity. Thus, there is a need for new target regions in Src that could inhibit Src activity only in certain cell types, e.g., cancer cells, while maintaining the normal physiological activity in healthy cells. The Src N-terminal regulatory element (SNRE) includes the poorly studied intrinsically disordered region with unique sequences for each of the members of the Src family. In this perspective, we discuss the non-canonical regulatory mechanisms involving the SNRE and their potential use as oncotargets. Impact Journals LLC 2023-05-19 /pmc/articles/PMC10197966/ /pubmed/37204272 http://dx.doi.org/10.18632/oncotarget.28434 Text en Copyright: © 2023 Mezquita et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Perspective
Mezquita, Betlem
Reyes-Farias, Marjorie
Pons, Miquel
Targeting the Src N-terminal regulatory element in cancer
title Targeting the Src N-terminal regulatory element in cancer
title_full Targeting the Src N-terminal regulatory element in cancer
title_fullStr Targeting the Src N-terminal regulatory element in cancer
title_full_unstemmed Targeting the Src N-terminal regulatory element in cancer
title_short Targeting the Src N-terminal regulatory element in cancer
title_sort targeting the src n-terminal regulatory element in cancer
topic Research Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197966/
https://www.ncbi.nlm.nih.gov/pubmed/37204272
http://dx.doi.org/10.18632/oncotarget.28434
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