Cathepsin S Mediates Gastric Cancer Cell Migration and Invasion via a Putative Network of Metastasis-Associated Proteins

作者：Yixuan Yang, Shen-Kiat Lim, Lee-Yee Choong, Huiyin Lee, Yunhao Chen, Poh‐Kuan Chong, Hassan Ashktorab, Ting Ting Wang, Manuel Salto‐Tellez, Khay Guan Yeoh, Yoon-Pin Lim · 发表于：Journal of Proteome Research · 年份：2010 · DOI：10.1021/pr101027g · 被引用次数：39 · 研究领域：Peptidase Inhibition and Analysis、Protease and Inhibitor Mechanisms、Biochemical and Structural Characterization

Cancer progression is governed by multifaceted interactions of cancer cells with their microenvironment and one of these ways is through secreted compounds. Substances released by gastric cancer cells have not being profiled in a proteome-wide manner. ITRAQ-based tandem mass spectrometry was employed to quantify proteins secreted by HFE145 normal, MKN7 well-differentiated, and MKN45 poorly differentiated gastric cancer cell lines. The expression levels of 237 proteins were found to be significantly different between normal and cancer cells. Further examination of 16 gastric cell lines and 115 clinical samples validated the up-regulation of CTSS expression in gastric cancer. Silencing CTSS expression suppressed the migration and invasion of gastric cancer cells <i>in vitro</i>. Subsequent secretomics revealed that CTSS silencing resulted in changes in expression levels of 197 proteins, one-third of which are implicated in cellular movement. Proteome-wide comparative secretomes of normal and gastric cancer cells were produced that constitute a useful resource for gastric cancer research. CTSS was demonstrated to play novel roles in gastric cancer cell migration and invasion, putatively via a network of proteins associated with cell migration, invasion, or metastasis. Cathepsin S is member of a large group of extracellular proteases, which are attractive drug targets. The implicated role of CTSS in gastric cancer metastasis provides an opportunity to test existing co...