Cell Signaling by a Novel SH2 Domain Protein that is Overexpressed with Her2 in Breast Cancer.

1996 ◽  
Author(s):  
Benjamin L. Margolis
Keyword(s):  
Breast Cancer ◽  
Cell Signaling ◽  
Sh2 Domain ◽  
Domain Protein

scholarly journals The SH2 domain protein GRB-7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer.

1994 ◽  
Vol 13 (6) ◽  
pp. 1331-1340 ◽  
Author(s):  
D. Stein ◽  
J. Wu ◽  
S.A. Fuqua ◽  
C. Roonprapunt ◽  
V. Yajnik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sh2 Domain ◽  
Domain Protein

scholarly journals The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 462
Author(s):  
Víctor Mayoral-Varo ◽  
María Pilar Sánchez-Bailón ◽  
Annarica Calcabrini ◽  
Marta García-Hernández ◽  
Valerio Frezza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Sh2 Domain ◽  
Model Systems ◽  
System A ◽  
Promising Therapeutic Target ◽  
Relevant Role ◽  
Inactivating Mutation

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.

scholarly journals Methyl-CpG binding domain protein 2 plays a causal role in breast cancer growth and metastasis

2020 ◽  
Author(s):  
Niaz Mahmood ◽  
Ani Arakelian ◽  
Moshe Szyf ◽  
Shafaat A. Rabbani
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Mammary Tumor ◽  
Tumor Burden ◽  
Tumor Formation ◽  
Binding Domain ◽  
Causal Role ◽  
Molecular Signaling ◽  
Primary Tumors ◽  
Domain Protein

AbstractMethyl-CpG-binding domain protein 2 (Mbd2), a reader of DNA-methylation, has been implicated in the progression of several types of malignancies, including breast cancer. To test whether Mbd2, which is overexpressed in human breast cancer samples and in MMTV-PyMT mammary pads, plays a causal role in mammary tumor growth and metastasis we depleted Mbd2 in transgenic MMTV-PyMT model of breast cancer by cross-breeding with Mbd2 knockout mice to generate heterozygous (PyMT;Mbd2+/-) and homozygous (PyMT;Mbd2-/-) animals. We found that Mbd2 depletion caused a gene dose-dependent delay in mammary tumor formation, reduced primary tumor burden, and lung metastasis at the experimental endpoint. In addition, animals from the PyMT;Mbd2-/- group survived significantly longer compared to the wildtype (PyMT;Mbd2+/+) and PyMT;Mbd2+/- arms. Transcriptomic and proteomic analyses of the primary tumors obtained from PyMT;Mbd2+/+ and PyMT;Mbd2+/- groups revealed that Mbd2 depletion alters several key determinants of the molecular signaling networks related to tumorigenesis and metastasis, which thereby demonstrate that Mbd2 is regulating transcriptional programs critical for breast cancer. To our knowledge, this is the first study demonstrating a causal role for a DNA-methylation reader in breast cancer. Results from this study will provide the rationale for further development of first-in-class targeted epigenetic therapies against Mbd2 to inhibit the progression of breast and other common cancers.

scholarly journals A Synthetic Triterpenoid CDDO-Im Inhibits Tumorsphere Formation by Regulating Stem Cell Signaling Pathways in Triple-Negative Breast Cancer

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107616 ◽  
Author(s):  
Jae Young So ◽  
Janice J. Lin ◽  
Joseph Wahler ◽  
Karen T. Liby ◽  
Michael B. Sporn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Signaling Pathways
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