Journal Article

The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy

Tong, Maomeng, Chang, Guodong, Luo, Yongzhang, Shi, Hubing, Song, Xiaomin, Fu, Yan, Zhuo, Wei, Liang, Yun, Wang, Xiaofeng

2009

Overview

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 Hsp90a 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. [PUBLICATION ABSTRACT]

• Publisher: National Academy of Sciences
• Subject: Kinases / Peptides / Plasma / Proteins / Tumors