Oncotarget

Research Perspectives:

Targeting the Src N-terminal regulatory element in cancer

Betlem Mezquita, Marjorie Reyes-Farias and Miquel Pons _

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Oncotarget. 2023; 14:503-513. https://doi.org/10.18632/oncotarget.28434

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Abstract

Betlem Mezquita1, Marjorie Reyes-Farias2 and Miquel Pons2

1 Biomolecular NMR Lab, Departament de Química Inorgànica i Orgànica, Universitat de Barcelona (UB), Barcelona 08028, Spain

2 Departament de Ciències Bàsiques, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès 08195, Spain

Correspondence to:

Miquel Pons, email: [email protected]

Keywords: Src family kinases; intrinsically disordered proteins; SNRE; cell-type selective drugs; drug resistance

Received: April 15, 2023     Accepted: May 05, 2023     Published: May 19, 2023

Copyright: © 2023 Mezquita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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