https://scholars.lib.ntu.edu.tw/handle/123456789/465958
標題: | An EGFR/Src-dependent β4 integrin/FAK complex contributes to malignancy of breast cancer | 作者: | Tai Y.-L. Chu P.-Y. I-RUE LAI Wang M.-Y. Tseng H.-Y. Guan J.-L. Liou J.-Y. Shen T.-L. |
公開日期: | 2015 | 出版社: | Nature Publishing Group | 卷: | 5 | 起(迄)頁: | 16408 | 來源出版物: | Scientific Reports | 摘要: | β4 integrin and focal adhesion kinase (FAK) are often associated with a poor prognosis in cancer patients, and their signaling events have recently been linked to malignant outcomes. Here, we demonstrate, for the first time, physical and functional interactions between β4 integrin and FAK that influence breast cancer malignancy. An amino-terminal linker within FAK is essential for its binding with the cytodomain of β4 integrin. Moreover, EGFR/Src-signaling triggers the tyrosine phosphorylation of β4 integrin, which, in turn, recruits FAK to β4 integrin and leads to FAK activation and signaling. Upon disruption of the β4 integrin/FAK complex, tumorigenesis and metastasis in triple-negative breast cancer were markedly reduced. Importantly, the concomitant overexpression of β4 integrin and FAK significantly correlates with malignant potential in patients with triple-negative breast cancer. This study describes a pro-metastatic EGFR/Src-dependent β4 integrin/FAK complex that is involved in breast cancer malignancy and is a novel therapeutic target for triple-negative breast cancer. ? 2015 Macmillan Publishers Limited. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946887740&doi=10.1038%2fsrep16408&partnerID=40&md5=0bede5af8df5a2424dd341904f33adfa https://scholars.lib.ntu.edu.tw/handle/123456789/465958 |
ISSN: | 2045-2322 | DOI: | 10.1038/srep16408 | SDG/關鍵字: | beta4 integrin; epidermal growth factor receptor; focal adhesion kinase; multiprotein complex; protein binding; protein kinase p60; animal; biological model; breast tumor; cell transformation; disease model; enzyme activation; female; genetics; human; metabolism; mouse; pathology; phosphorylation; signal transduction; triple negative breast cancer; tumor cell line; xenograft; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Transformation, Neoplastic; Disease Models, Animal; Enzyme Activation; Female; Focal Adhesion Protein-Tyrosine Kinases; Heterografts; Humans; Integrin beta4; Mice; Models, Biological; Multiprotein Complexes; Phosphorylation; Protein Binding; Proto-Oncogene Proteins pp60(c-src); Receptor, Epidermal Growth Factor; Signal Transduction; Triple Negative Breast Neoplasms |
顯示於: | 解剖學暨細胞生物學科所 |
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