title: Cathepsin S mediates gastric cancer cell migration and invasion via a putative network of metastasis-associated proteins.
abstract: 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 in vitro. 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 compounds against CTSS for adjuvant therapy and/or treatment of metastatic gastric cancers.
authors.affiliation: Cancer Science Institute of Singapore, Department of Medicine, National University of Singapore, Singapore.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yixuan
authors.forename: Shen-Kiat
authors.initials: SK
authors.lastname: Lim
authors.forename: Lim Shen
authors.initials: LS
authors.lastname: Kiat
authors.forename: Lee-Yee
authors.initials: LY
authors.lastname: Choong
authors.forename: Choong Lee
authors.initials: CL
authors.lastname: Yee
authors.forename: Huiyin
authors.initials: H
authors.lastname: Lee
authors.forename: Lee
authors.initials: L
authors.lastname: Huiyin
authors.forename: Yunhao
authors.initials: Y
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Yunhao
authors.forename: Poh-Kuan
authors.initials: PK
authors.lastname: Chong
authors.forename: Chong Poh
authors.initials: CP
authors.lastname: Kuan
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.forename: Ashktorab
authors.initials: A
authors.lastname: Hassan
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Wang
authors.forename: Wang Ting
authors.initials: WT
authors.lastname: Ting
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: Salto-Tellez
authors.initials: ST
authors.lastname: Manuel
authors.forename: Khay-Guan
authors.initials: KG
authors.lastname: Yeoh
authors.forename: Yeoh Khay
authors.initials: YK
authors.lastname: Guan
authors.forename: Yoon-Pin
authors.initials: YP
authors.lastname: Lim
authors.forename: Lim Yoon
authors.initials: LY
authors.lastname: Pin
mesh_terms: D002403:Cathepsins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D007553:Isotope Labeling; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053719:Tandem Mass Spectrometry
chemical_list: D009363:Neoplasm Proteins; D002403:Cathepsins; C028217:cathepsin S