論文 - 詳細
| RRC ID | 68021 |
|---|---|
| 著者 | Kariya Y, Oyama M, Hashimoto Y, Gu J, Kariya Y. |
| タイトル | β4-Integrin/PI3K Signaling Promotes Tumor Progression through the Galectin-3-N-Glycan Complex. |
| ジャーナル | Mol Cancer Res |
| Abstract |
Malignant transformation is associated with aberrant N-glycosylation, but the role of protein N-glycosylation in cancer progression remains poorly defined. β4-integrin is a major carrier of N-glycans and is associated with poor prognosis, tumorigenesis, and metastasis. Here, N-glycosylation of β4-integrin contributes to the activation of signaling pathways that promote β4-dependent tumor development and progression. Increased expression of β1,6GlcNAc-branched N-glycans was found to be colocalized with β4-integrin in human cutaneous squamous cell carcinoma tissues, and that the β1,6GlcNAc residue was abundant on β4-integrin in transformed keratinocytes. Interruption of β1,6GlcNAc-branching formation on β4-integrin with the introduction of bisecting GlcNAc by N-acetylglucosaminyltransferase III overexpression was correlated with suppression of cancer cell migration and tumorigenesis. N-Glycan deletion on β4-integrin impaired β4-dependent cancer cell migration, invasion, and growth in vitro and diminished tumorigenesis and proliferation in vivo The reduced abilities of β4-integrin were accompanied with decreased phosphoinositol-3 kinase (PI3K)/Akt signals and were restored by the overexpression of the constitutively active p110 PI3K subunit. Binding of galectin-3 to β4-integrin via β1,6GlcNAc-branched N-glycans promoted β4-integrin-mediated cancer cell adhesion and migration. In contrast, a neutralizing antibody against galectin-3 attenuated β4-integrin N-glycan-mediated PI3K activation and inhibited the ability of β4-integrin to promote cell motility. Furthermore, galectin-3 knockdown by shRNA suppressed β4-integrin N-glycan-mediated tumorigenesis. These findings provide a novel role for N-glycosylation of β4-integrin in tumor development and progression, and the regulatory mechanism for β4-integrin/PI3K signaling via the galectin-3-N-glycan complex.Implications:N-Glycosylation of β4-integrin plays a functional role in promoting tumor development and progression through PI3K activation via the galectin-3-N-glycan complex. Mol Cancer Res; 16(6); 1024-34. ©2018 AACR. |
| 巻・号 | 16(6) |
| ページ | 1024-1034 |
| 公開日 | 2018-6-1 |
| DOI | 10.1158/1541-7786.MCR-17-0365 |
| PII | 1541-7786.MCR-17-0365 |
| PMID | 29549127 |
| MeSH | Animals Blood Proteins Cell Adhesion Cell Line, Tumor Cell Movement Disease Progression Female Galectin 3 / metabolism* Galectins Humans Integrin beta4 / metabolism* Mice Mice, Nude Phosphatidylinositol 3-Kinases / metabolism* Signal Transduction |
| IF | 4.63 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A431(RCB0202) |