The Regulatory Mechanism of Extracellular Hsp90α on Matrix Metalloproteinase-2 Processing and Tumor Angiogenesis

• DOI: 10.1074/jbc.m110.181941
• Publication Date: 2010-10-12T05:25:21Z
• Authors: Xiaomin Song; Xiaofeng Wang; Wei Zhuo; Hubing Shi; Dan Feng; Yi Sun; Yun Liang; Yan Fu; Daifu Zhou; Yongzhang Luo
• Keywords: Matrigel

Heat shock protein 90α (Hsp90α) is a ubiquitously expressed molecular chaperone that essential for eukaryotic homeostasis. Hsp90α can also be secreted extracellularly, where it has been shown to involved in tumor metastasis. Extracellular interacts with and promotes the proteolytic activity of matrix metalloproteinase-2 (MMP-2). However, regulatory mechanism on MMP-2 still unknown. Here we show stabilizes protects from degradation cells. Further investigation reveals this stabilization effect isoform-specific, ATP-independent, mediated by interaction between middle domain C-terminal hemopexin domain. Moreover, applies endothelial cells secrete more their proliferating status. Furthermore, cell transmigration, Matrigel plug, angiogenesis assays demonstrate extracellular an MMP-2-dependent manner. In sum, study provides new insights into how regulates its client proteins first time function promoting angiogenesis.