The Kinase LMTK3 Promotes Invasion in Breast Cancer Through GRB2-Mediated Induction of Integrin β 1
| العنوان: | The Kinase LMTK3 Promotes Invasion in Breast Cancer Through GRB2-Mediated Induction of Integrin β 1 |
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| المؤلفون: | Maya Thanou, Yichen Xu, A. Grothey, Maria Athanasiadou, Simak Ali, Georgios Giamas, Marianna Kiritsi, Heinz-Josef Lenz, Andrew R. Green, Adam E Frampton, Justin Stebbing, Ylenia Lombardo, L C Lit, Ian O. Ellis, Hua Zhang |
| المصدر: | Science Signaling. 7 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | biology, PTK2, Integrin, GRB7, Cell Biology, Biochemistry, Collagen receptor, Integrin alpha M, Alpha-5 beta-1, biology.protein, Cancer research, Lemur tyrosine kinase 3, Integrin, beta 6, Molecular Biology |
| الوصف: | Lemur tyrosine kinase 3 (LMTK3) is associated with cell proliferation and endocrine resistance in breast cancer. We found that, in cultured breast cancer cell lines, LMTK3 promotes the development of a metastatic phenotype by inducing the expression of genes encoding integrin subunits. Invasive behavior in various breast cancer cell lines positively correlated with the abundance of LMTK3. Overexpression of LMTK3 in a breast cancer cell line with low endogenous LMTK3 abundance promoted actin cytoskeleton remodeling, focal adhesion formation, and adhesion to collagen and fibronectin in culture. Using SILAC (stable isotope labeling by amino acids in cell culture) proteomic analysis, we found that LMTK3 increased the abundance of integrin subunits α5 and β1, encoded by ITGA5 and ITGB1. This effect depended on the CDC42 Rho family guanosine triphosphatase, which was in turn activated by the interaction between LMTK3 and growth factor receptor-bound protein 2 (GRB2), an adaptor protein that mediates receptor tyrosine kinase-induced activation of RAS and downstream signaling. Knockdown of GRB2 suppressed LMTK3-induced CDC42 activation, blocked ITGA5 and ITGB1 expression promoted by the transcription factor serum response factor (SRF), and reduced invasive activity. Furthermore, abundance of LMTK3 positively correlated with that of the integrin β1 subunit in breast cancer patient's tumors. Our findings suggest a role for LMTK3 in promoting integrin activity during breast cancer progression and metastasis. |
| تدمد: | 1937-9145 1945-0877 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::36396096bdb1562e10e9203fd15d8c3c https://doi.org/10.1126/scisignal.2005170 |
| رقم الأكسشن: | edsair.doi...........36396096bdb1562e10e9203fd15d8c3c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19379145 19450877 |
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