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

doi:10.1016/j.yexcr.2014.05.018

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

Exp Cell Res. 2014 Aug 1;326(1):78-89. doi: 10.1016/j.yexcr.2014.05.018. Epub 2014 May 28.

Authors

Xiangyang Xiong¹, Yao Wang², Chengmei Liu³, Quqin Lu⁴, Tao Liu², Guoan Chen⁵, Hai Rao⁶, Shiwen Luo⁷

Affiliations

¹ 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.
² Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006, China.
³ State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
⁴ Department of Biostatistics & Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006, China.
⁵ Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
⁶ Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.
⁷ Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006, China. Electronic address: shiwenluo@ncu.edu.cn.

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.

Keywords: Breast cancer; FAK; HSP90β; Metastasis; Ubiquitin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Blotting, Western
Cell Adhesion
Cell Movement*
Cell Proliferation
Cytoskeleton / metabolism
Female
Fluorescent Antibody Technique
Focal Adhesion Kinase 1 / chemistry
Focal Adhesion Kinase 1 / genetics
Focal Adhesion Kinase 1 / metabolism*
Humans
Immunoenzyme Techniques
Immunoprecipitation
Membrane Glycoproteins / antagonists & inhibitors
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism*
Neoplasm Invasiveness
Phosphorylation
Proteolysis
RNA, Small Interfering / genetics
Signal Transduction
Tumor Cells, Cultured
Ubiquitin / metabolism*
Ubiquitination

Substances

Membrane Glycoproteins
RNA, Small Interfering
Ubiquitin
endoplasmin
Focal Adhesion Kinase 1
PTK2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding