Knockdown of C1GalT1 inhibits radioresistance of human esophageal cancer cells through modifying β1-integrin glycosylation.
Knockdown of C1GalT1 inhibits radioresistance of human esophageal cancer cells through modifying β1-integrin glycosylation.
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C1GalT1 的敲低通过修饰 β1-整合素糖基化抑制人食管癌细胞的放射抗性
DOI：
10.7150/jca.25252
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发表时间：
2018
影响因子：
3.9
通讯作者：
Luo Z
中科院分区：
文献类型：
--
作者：
Zhang C;Deng X;Qiu L;Peng F;Geng S;Shen L;Luo Z
由于肿瘤放射抵抗的风险，放射治疗在人类食管癌的治疗中发挥了有限的作用。核心1 β1，3-半乳糖基转移酶（C1 GalT 1）催化核心1 O-聚糖结构的形成，在肿瘤发生过程中经常过表达。然而，C1 GalT 1在食管癌放射抵抗中的确切作用和机制尚不清楚。在这项研究中，公共数据库和我们的数据显示，C1 GalT 1表达上调食管癌组织，并与生存率低。照射后，我们发现具有高水平C1 GalT 1的食管癌细胞可以耐受细胞死亡，并且对放射治疗的抵抗力增加。辐射还促进C1 GalT 1和核心1 O-聚糖结构的表达。C1 GalT 1基因敲低增加了食管癌细胞的放射敏感性，并减弱了放射增强的迁移和侵袭。机制研究表明，C1 GalT 1修饰β1-integrin上的O-聚糖结构，调节其下游粘着斑激酶（focal adhesion kinase，FAK）信号通路。β1-整合素阻断抗体和FAK抑制剂可增强辐射诱导的食管癌细胞凋亡。总之，我们的结果表明C1 GalT 1是通过调节β1-整联蛋白糖基化而产生辐射抗性的主要决定因素。C1 GalT 1可能是增强放射治疗疗效的有效分子靶点。
Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 β1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival. Upon irradiation, we found that esophageal cancer cells with high levels of C1GalT1 could tolerate cell death and had increased resistance to radiotherapy. Irradiation also promoted the expression of C1GalT1 and core 1 O-glycan structures. C1GalT1 knockdown increased the radiosensitivity of esophageal cancer cells, and attenuated irradiation-enhanced migration and invasion. Mechanistic investigations showed that C1GalT1 modified O-glycan structures on β1-integrin and regulated its downstream focal adhesion kinase (FAK) signaling. Furthermore, β1-integrin-blocking antibody and FAK inhibitor enhanced radiation-induced apoptosis in esophageal cancer cells. Together, our results indicate that C1GalT1 is a major determinant of radioresistance via modulation of β1-integrin glycosylation. C1GalT1 may be a potent molecular target for enhancing the efficacy of radiotherapy.
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影响因子：
4.6
作者：
Guan, Jun-Lin
通讯作者：
Guan, Jun-Lin
O-糖基化改变与人类喉癌固有的放射抗性和恶性有关
影响因子：
3.7
作者：
Dong, Xiaoxia;Luo, Zhiguo;Shen, Li
通讯作者：
Shen, Li
影响因子：
5.2
作者：
Lee, Minyoung;Lee, Hae-June;Lee, Yun-Sil
通讯作者：
Lee, Yun-Sil
影响因子：
3.4
作者：
Kong, Lingying;Du, Wei;Lin, Donghong
通讯作者：
Lin, Donghong
DOI：
10.1007/978-1-4614-4989-8_21
发表时间：
2013-01-01
期刊：
OXYGEN TRANSPORT TO TISSUE XXXIV
影响因子：
--
作者：
Ma, Jun;Han, Deping;Zhang, Lurong
通讯作者：
Zhang, Lurong