Earticle

초록

영어

Sialic acids are widely distributed in nature as terminal sugars attached to glycoproteins and glycolipids. The biosynthesis of this molecule is important for activity of carbohydrate-binding proteins including lectins, antibodies, and receptors. Among sialyltransferases, β-Galactoside α2, 6-sialyltransferase (ST6Gal-I) has been responsible for α2, 6-sialylation of N-Glycan,an action that is highly correlated with colon cancer progression and metastasis. We have previously demonstrated that ST6 Gal-I-induced α2, 6 sialylation contributes to enhancement of cell migration and radio resistance of colon cancer. A number of studies have focused on the involvement of sialylation in tumorigenesis, but the mechanism underlying ST6Gal-I-induced cancer progression and the identity of enzyme substrates has received scant research attention. To provide further support for the relevance of ST6Gal-I in the malignancy of colon cancer, we prepared and characterized a ST6Gal-I-knockdown SW480 colorectal carcinoma cell line. We found that inhibition of ST6Gal-I expression increased cell proliferation and tumor growth in vitro and in vivo. An examination of the effect of sialylation on epidermal growth factor receptor (EGFR) activity and downstream signaling, which are highly correlated with cell proliferation, showed that the loss of ST6Gal-I augmented EGF-induced EGFR phosphorylation and activation of extracellular signal-regulated kinase (ERK) in colon cancer cells. Moreover, ST6Gal-I induced sialylationof both wild type and mutant EGFR. These studies provide the first demonstration that ST6Gal-I induces EGFR sialylation in human colon cancer cell lines. Importantly, the anticancer effect of the EGFR kinase inhibitor, gefitinib, was increased in ST6Gal-I-deficient colon cancer cells. In contrast, overexpression of ST6Gal I decreased the cytotoxic effect of gefitinib. These results suggest that sialylation of the EGFR affects EGF-mediated cell growth and down regulates sensitivityto gefitinib in colon cancer cells.

저자

• Jung-Jin Park [ Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea ]
• Jae-Youn Yi [ Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences ]
• Jin-Hong Kim [ Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences ]
• Yoon-Jin Lee [ Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences ]
• Young-Gyu Ko [ College of Life Sciences and Biotechnology, Korea University, Seoul, Korea ]
• Minyoung Lee [ Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences ]

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간행물

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• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614