Open AccessThe regulatory mechanism of Hsp90α secretion and its function in tumor malignancy
Author(s) -
Xiaofeng Wang,
Xiaomin Song,
Wei Zhuo,
Yan Fu,
Hubing Shi,
Yun Liang,
ManLi Tong,
Guodong Chang,
Yongzhang Luo
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0908151106
Subject(s) - secretion , tetratricopeptide , heat shock protein , hsp90 , endocrinology , medicine , malignancy , chemistry , immunoprecipitation , function (biology) , biology , biochemistry , microbiology and biotechnology , gene
Heat shock protein 90-α (Hsp90α) is an intracellular molecular chaperone. However, it can also be secreted with the underlying regulatory mechanism remaining far from clear. Here we show that the secreted Hsp90α is a C-terminal truncated form and its secretion is regulated by the C-terminal EEVD motif via interacting with proteins containing tetratricopeptide repeat domains. We also demonstrate that secretion of Hsp90α is determined by the phosphorylation status at residue Thr-90, regulated by protein kinase A and protein phosphatase 5. We further demonstrate that the secretion of Hsp90α is a prerequisite for its proinvasiveness function and blocking the secreted Hsp90α results in significant inhibition of tumor metastasis. Meanwhile, the level of plasma Hsp90α is positively correlated with tumor malignancy in clinical cancer patients. In sum, our results reveal the regulatory mechanism of Hsp90α secretion, and its function in tumor invasiveness, indicating it can be a promising diagnostic marker for tumor malignancy in clinical application.