Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells.

Xiangyang Xiong, Yao Wang, Chengmei Liu, Quqin Lu, Tao Liu, Guoan Chen, Hai Rao, Shiwen Luo

Journal: Experimental cell research 2014;326(1):78-89

PMID: 24880126

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Abstract

Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233-620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer.

Address: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006, China; Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006, China; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.; Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006, China.; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.; Department of Biostatistics & Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006, China.; Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.; Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.; Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006, China. Electronic address: [email protected].

DOI: 10.1016/j.yexcr.2014.05.018

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MeSH Terms: Apoptosis, Blotting, Western, Cell Adhesion, Cell Movement, Cell Proliferation, Cytoskeleton, Female, Fluorescent Antibody Technique, Focal Adhesion Kinase 1, Humans, Immunoenzyme Techniques, Immunoprecipitation, Membrane Glycoproteins, Neoplasm Invasiveness, Phosphorylation, Proteolysis, RNA, Small Interfering, Signal Transduction, Tumor Cells, Cultured, Ubiquitin, Ubiquitination