β-1,4-Galactosyltransferase III suppresses β1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer
β-1,4-Galactosyltransferase III suppresses β1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer
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DOI：
10.1093/carcin/bgu007
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发表时间：
2014-06-01
期刊：
影响因子：
4.7
通讯作者：
Huang, Min-Chuan
中科院分区：
文献类型：
--
作者：
Chen, Chia-Hua;Wang, Shui-Hua;Huang, Min-Chuan
结直肠癌患者常发生转移，是肿瘤治疗的主要难点。在CRC患者中发现聚-N-乙酰乳糖胺相关糖基化的上调，并且与癌症的进展和转移相关。β-1，4-半乳糖基转移酶III（B4 GALT 3）是负责聚-N-乙酰乳糖胺合成的酶，因此，我们研究了其在CRC患者中的表达。B4 GALT 3与大肠癌组织学分化（P < 0.001）、临床分期（P = 0.0052）、淋巴结转移（P = 0.0018）和远处转移（P = 0.0463）呈负相关。B4 GALT 3在CRC细胞中的过表达抑制细胞迁移、侵袭和粘附，而B4 GALT 3敲低增强恶性细胞表型。β 1整合素阻断抗体逆转了B4 GALT 3介导的细胞侵袭增加。B4 GALT 3表达可能通过改变聚-N-乙酰乳糖胺表达改变β 1整联蛋白N-聚糖上的糖基化。此外，在B4 GALT 3敲低的细胞中发现更多的活化的β 1整合素沿着其下游信号转导的活化，而B4 GALT 3的过表达抑制活性β 1整合素的表达并抑制其下游信号转导。我们的研究结果表明，B4 GALT 3与结直肠癌转移呈负相关，并通过抑制β 1整合素的活化来抑制细胞侵袭。
Metastasis often occurs in colorectal cancer (CRC) patients and is the main difficulty in cancer treatment. The upregulation of poly-N-acetyllactosamine-related glycosylation is found in CRC patients and is associated with progression and metastasis in cancer. beta-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for poly-N-acetyllactosamine synthesis, and therefore, we investigated its expression in CRC patients. We found that B4GALT3 negatively correlated with poorly differentiated histology (P < 0.001), advanced stages (P = 0.0052), regional lymph node metastasis (P = 0.0018) and distant metastasis (P = 0.0463) in CRC patients. B4GALT3 overexpression in CRC cells suppressed cell migration, invasion and adhesion, whereas B4GALT3 knockdown enhanced malignant cell phenotypes. The beta 1 integrin-blocking antibody reversed the B4GALT3-mediated increase in cell invasion. B4GALT3 expression altered glycosylation on the N-glycan of beta 1 integrin probably through changes in poly-N-acetyllactosamine expression. Furthermore, more activated beta 1 integrin along with the activation of its downstream signaling transduction were found in B4GALT3 knockdown cells, whereas overexpression of B4GALT3 suppressed the expression of active beta 1 integrin and inhibited its downstream signaling. Our results suggest that B4GALT3 is negatively associated with CRC metastasis and suppresses cell invasiveness through inhibiting activation of beta 1 integrin.