title: An EGFR/Src-dependent β4 integrin/FAK complex contributes to malignancy of breast cancer.
abstract: 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.
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Tai
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chu
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.|Department of Surgery, National Taiwan University Hospital, Taipei 10048, Taiwan.
authors.forename: I-Rue
authors.initials: IR
authors.lastname: Lai
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei 10048, Taiwan.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Tseng
authors.affiliation: Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 10617, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D039663:Integrin beta4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D039663:Integrin beta4; D046912:Multiprotein Complexes; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)