The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells
| Autor: | Víctor Mayoral-Varo, Marta García-Hernández, María Pilar Sánchez-Bailón, Víctor M. González, María Elena Martín, Jorge Martín-Pérez, Annarica Calcabrini, Valerio Frezza |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Population c-Src aptamers Biology medicine.disease_cause SH2 domain Aptamers lcsh:RC254-282 Article triple-negative breast cancer (TNBC) 03 medical and health sciences 0302 clinical medicine Triple-negative breast cancer (TNBC) medicine education Triple-negative breast cancer Inactivating point mutation education.field_of_study Kinase inactivating point mutation Transfection lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Carcinogenesis Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Cancers, Vol 13, Iss 462, p 462 (2021) Cancers Volume 13 Issue 3 Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2072-6694 |
| Popis: | The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems. These cells conditionally expressed, under tetracycline control (Tet-On system), a c-Src variant with point-inactivating mutation of the SH2 adapter domain (R175L). The expression of this mutant reduced the self-renewal capability of the enriched population of breast cancer stem cells (BCSCs), demonstrating the importance of the SH2 adapter domain of c-Src in the mammary gland carcinogenesis. In addition, the analysis of anchorage-independent growth, proliferation, migration, and invasiveness, all processes associated with tumorigenesis, showed that the SH2 domain of c-Src plays a very relevant role in their regulation. Furthermore, the transfection of two different aptamers directed to SH2-c-Src in both SUM159PT and MDA-MB-231 cells induced inhibition of their proliferation, migration, and invasiveness, strengthening the hypothesis that this domain is highly involved in TNBC tumorigenesis. Therefore, the SH2 domain of c-Src could be a promising therapeutic target and combined treatments with inhibitors of c-Src kinase enzymatic activity may represent a new therapeutic strategy for patients with TNBC, whose prognosis is currently very negative. This work and the salary of Víctor Mayoral-Varo have been supported by grant number SAF2016–75991-R (MINECO, AEI/FEDER, UE) to Jorge Martín-Pérez. |
| Databáze: | OpenAIRE |
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