RECK-mediated suppression of tumor cell invasion is regulated by glycosylation in human tumor cell lines (Cancer Res., 65:7455-7461, 15 August 2005)

報告日期: 2005/10/14
報告時間: 17:10/18:00
報告學生: 翁汶燦
講評老師: 賴明德
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RECK-Mediated Suppression of Tumor Cell Invasion Is Regulated by Glycosylation in Human Tumor Cell Lines

Cancer Research 65, 7455-7461, 2005

Speaker : 翁汶燦                        Time : Oct. 14, 2005, 17:10-1800

Commentator : 賴明德 教授               Place: Room 602

 

Abstract:

    RECK (Reversion-inducing cysteine-rich protein with Kazal motifs) is a membrane-anchored glycoprotein that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumor invasion and metastasis1-3.  Human RECK was predicted to have five putative N-glycosylation sites at Asn39, Asn86, Asn200, Asn297 and Asn352 residues.  At present, many of the functions of protein glycosylation have been known, including secretion to the extracellular space, the promotion of protein activation, and stabilization of glycoproteins.  But the biochemical roles played by glycosylation in the function of RECK has not yet been investigated.  In this study, the authors clarify the glycosylation roles in the function of RECK in human tumor cell lines. They found N-glycosylation does indeed occur at the Asn86, Asn200, Asn297 and Asn352 residues but not at the Asn39 residue of RECK. However the glycosylation of RECK is not required for the cell surface localization of RECk as a glycosylphosphatidylinositol-anchored protein. Interestingly, the glycosylation of RECK Asn297 and Asn352 residues is involved in the suppression of MMP-9 secretion and of MMP-2 activation, respectively. Furthermore, the circumvention of RECK-suppressed tumor cell invasion by inhibiting glycosylation at Asn39, Asn297 and Asn352 residues. Therefore, glycosylation of RECK plays an important role in the function of RECK-inhibited tumor cell invasion. And glycosylated RECK regulates tumor cell invasion by multiple mechanisms excluding suppression of MMP-9

secretion and of MMP-2 activation.

 

 

1.         Noda, M. et al. RECK: a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. Cancer Metastasis Rev 22, 167-75 (2003).

2.         Sasahara, R. M., Takahashi, C., Sogayar, M. C. & Noda, M. Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene. Braz J Med Biol Res 32, 891-5 (1999).

3.         Oh, J. et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107, 789-800 (2001).