Cathepsin S mediates gastric cancer cell migration and invasion via a putative network of metastasis-associated proteins.
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.
Yang
Yixuan
Y
Cancer Science Institute of Singapore, Department of Medicine, National University of Singapore, Singapore.
Yixuan
Yang
Y
Lim
Shen-Kiat
SK
Kiat
Lim Shen
LS
Choong
Lee-Yee
LY
Yee
Choong Lee
CL
Lee
Huiyin
H
Huiyin
Lee
L
Chen
Yunhao
Y
Yunhao
Chen
C
Chong
Poh-Kuan
PK
Kuan
Chong Poh
CP
Ashktorab
Hassan
H
Hassan
Ashktorab
A
Wang
Ting Ting
TT
Ting
Wang Ting
WT
Salto-Tellez
Manuel
M
Manuel
Salto-Tellez
ST
Yeoh
Khay-Guan
KG
Guan
Yeoh Khay
YK
Lim
Yoon-Pin
YP
Pin
Lim Yoon
LY
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
D009363:Neoplasm Proteins; D002403:Cathepsins; C028217:cathepsin S