ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway.
ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway.
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DOI：
10.18632/oncotarget.22545
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发表时间：
2017-12-22
期刊：
影响因子：
--
通讯作者：
Torigoe T
中科院分区：
文献类型：
--
作者：
Ogawa T;Hirohashi Y;Murai A;Nishidate T;Okita K;Wang L;Ikehara Y;Satoyoshi T;Usui A;Kubo T;Nakastugawa M;Kanaseki T;Tsukahara T;Kutomi G;Furuhata T;Hirata K;Sato N;Mizuguchi T;Takemasa I;Torigoe T
结直肠癌（Colorectal cancer，CRC）是一种因治疗抵抗、复发和远处转移而致死的疾病。新的证据表明，一小部分被称为癌症干细胞（cancer stem cells，CSC）/癌症起始细胞（cancer initiating cells，CIC）的癌细胞亚群被赋予高水平的肿瘤起始能力、自我更新能力和分化能力，并且负责治疗抗性、复发和远处转移。CSCs/CIC的根除对于改善目前的治疗至关重要。然而，CSC/CIC维持的分子机制仍然是难以捉摸的。在这项研究中，我们的目的是确定结肠直肠（CR）-CSC/CIC维持人类原代CRC细胞的分子机制。通过球形培养和ALDEFLUOR测定分离CR-CSC/CIC，并且转录组分析显示基因ST 6 N-乙酰氨基半乳糖α-2，6-唾液酸转移酶1（ST 6 GALNAC 1）在CR-CSC/CIC中以高水平表达。ST 6 GALNAC 1的过表达增强了CSC标志物CD 44携带的唾液酸-Tn（STn）抗原的表达，并增加了球体形成能力和对化疗试剂的抗性。通过使用siRNA的基因敲低观察到相反的现象。此外，Akt通路在ST 6 GANAC 1过表达的细胞中被激活，并且该通路的激活通过半乳糖凝集素-3的基因敲低而被取消。结果表明，ST 6 GALNAC 1通过与半乳糖凝集素-3协同激活Akt通路在CR-CSC/CIC的维持中起作用，并且ST 6 GalNAC 1（或STn抗原）可能是CSC/CIC靶向治疗的合理分子。
Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive. In this study, we aimed to determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and increased the sphere-forming ability and resistance to a chemotherapeutic reagent. The opposite phenomena were observed by gene knockdown using siRNA. Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and activation of the pathway was cancelled by gene knockdown of galectin-3. The results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
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影响因子：
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通讯作者：
Santos LL