Background: Cysteine proteases like cathepsins are widely distributed proteolytic enzymes and form tight equimolar complexes with cystatins at their active sites. Among cystatins, CST1, encoding cystatin SN, is a member of the type 2 salivary cystatin family found in a variety of fluids and secretions, including plasma, tears, and saliva. CST1 was identified as an upregulated gene in gastric cancer tissues compared to noncancerous regions using our Affymetrix GeneChip microarray. Methods: The upregulation of CST1 in gastric cancer was analyzed using RT-PCR (n = 15), immnohistochemistry, and clinicopathological (n = 77) analysis. CST1-siRNA was used for the suppression of CST1 gene expression and cathepsin proteolytic activity was assayed. Results: CST1 was upregulated in cancerous lesions of gastric cancer tissues compared to noncancerous regions and clinicopathological analysis showed a significant correlation between high expression of CST1 and pTNM stage (p = 0.044). In CST1-siRNA transfected cells, cell proliferation was reduced and the proteolytic activity of cathepsins was increased. Conclusions: CST1 might be highly involved in gastric tumorigenesis and regulate the proteolytic activity of cysteine proteases. Crown
Bibliographical noteFunding Information:
This work was supported by FG09-12-01 of the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea, and by the KRIBB Research Initiative Program.
- Cystatin SN
- Gastric cancer
ASJC Scopus subject areas
- Clinical Biochemistry
- Biochemistry, medical