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

Journal Article · Fri Aug 01 04:00:00 EDT 2014 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2014.05.018· OSTI ID:22416913

Xiong, Xiangyang ^[1]; Wang, Yao ^[1]; Liu, Chengmei ^[2]; Lu, Quqin ^[3]; Liu, Tao ^[1]; Chen, Guoan ^[4]; Rao, Hai ^[5]; Luo, Shiwen ^[1]

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1. Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China)
2. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China)
3. Department of Biostatistics and Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006 (China)
4. Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006 (China)
5. Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229 (United States)

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. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton.

• OSTI ID: 22416913
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 326; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
AMINO ACIDS
CELL PROLIFERATION
HEAT-SHOCK PROTEINS
MAMMARY GLANDS
MICROTUBULES
NEOPLASMS
TUMOR CELLS