Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

The relevance of the SH2 domain for c-Src functionality in triple-negative breast cancer cells

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB
[thumbnail of Supplementary Material]
Preview
PDF (Supplementary Material) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB

Item Type:Article
Title:The relevance of the SH2 domain for c-Src functionality in triple-negative breast cancer cells
Creators Name:Mayoral-Varo, V., Sánchez-Bailón, M.P., Calcabrini, A., García-Hernández, M., Frezza, V., Martín, M.E., González, V.M. and Martín-Pérez, J.
Abstract: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.
Keywords:Triple-Negative Breast Cancer (TNBC), c-Src, SH2 Domain, Inactivating Point Mutation, Aptamers
Source:Cancers
ISSN:2072-6694
Publisher:MDPI
Volume:13
Number:3
Page Range:462
Date:26 January 2021
Official Publication:https://doi.org/10.3390/cancers13030462
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library