β1,4-N-acetylgalactosaminyltransferase III enhances malignant phenotypes of colon cancer cells
β1,4-N-acetylgalactosaminyltransferase III enhances malignant phenotypes of colon cancer cells
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DOI：
10.1158/1541-7786.mcr-06-0431
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发表时间：
2007-06-01
影响因子：
5.2
通讯作者：
Huang, Min-Chuan
中科院分区：
文献类型：
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作者：
Huang, John;Liang, Jin-Tung;Huang, Min-Chuan
酶01，β1，4-N-乙酰半乳糖胺-尼基转移酶III(β4GMNAc-T3)在体外具有合成N，N‘-二乙酰乳糖二胺，GaINAcβ1，4GIcNAc的活性。在这里，我们研究了β4GaINAc-T3在原发结肠肿瘤中的表达及其过表达对HCT16结肠癌细胞的影响。实时荧光定量逆转录-聚合酶链式反应显示，72.5%(n=40)的原发结肠癌组织中β4GaINAc-T3表达上调。β4GaINAc-T3过表达导致细胞-细胞外基质黏附、迁移、非锚定细胞生长和结肠癌细胞侵袭能力增强。此外，β4GaINAc-T3过表达增加了肿瘤的生长和转移，并降低了荷瘤裸鼠的生存时间。β4GaINAc-T3过表达表现为粘着斑激酶和Paxlin Y118的酪氨酸磷酸化增加，以及细胞外信号调节激酶的磷酸化增加。这些结果表明，β4Ga1NAc-T3的上调可能在促进肿瘤恶性过程中起关键作用，整合素和丝裂原激活的蛋白激酶信号通路可能参与了其潜在的机制。
The enzyme 01,beta 1,4-N-acetylgalactosam i nyltransf erase III (beta 4GMNAc-T3) exhibits in vitro activity of synthesizing N,N '-diacetyllactosediamine, GaINAc beta 1,4GIcNAc. Here, we investigate the expression of beta 4GaINAc-T3 in primary colon tumors and the effects of its overexpression on HCT1 16 colon cancer cells. Real-time reverse transcription-PCR showed that the expression of beta 4GaINAc-T3 was up-regulated in 72.5% (n = 40) of primary colon tumors compared with their normal counterparts. beta 4GaINAc-T3 overexpression resulted in enhanced cell-extracellular matrix adhesion, migration, anchorage-independent cell growth, and invasion of colon cancer cells. Moreover, beta 4GaINAc-T3 overexpression increased tumor growth and metastasis and decreased survival of tumor-bearing nude mice. beta 4GaINAc-T3 overexpression showed increased tyrosine phosphorylation of focal adhesion kinase and paxillin Y118 as well as increased extracellular signal-regulated kinase phosphorylation. These results suggest that up-regulation of beta 4Ga1NAc-T3 may play a critical role in promoting tumor malignancy and that integrin and mitogen-activated protein kinase signaling pathways could be involved in the underlying mechanism.