Guangxi Colleges and Universities Key Laboratory of Pharmacology, Guilin Medical University, Guilin 541004, China.
Aging (Albany NY). 2022 Jun 9;14(11):4858-4873. doi: 10.18632/aging.204116.
The roles of asparagine-linked glycosylation (ALG) members in tumorigenic process have been widely explored. However, their effects in colorectal cancer progression are still confusing. Here, we screened 12 ALGs' expression through online datasets and found that was mostly upregulated in colorectal cancer tissues. We found that knockdown significantly suppressed the expression of stemness markers, ALDH activity, and sphere-formation ability. tumorigenic analysis indicated that knockdown attenuated the tumor-initiating ability and chemoresistance of colorectal cancer cells. Further mechanistic studies showed that knockdown suppressed the activity of TGF-β signaling by reducing TGFBR2 glycosylation, which was necessary for -mediated effects on colorectal cancer stemness; Conversely, TGF-β signaling activated gene promoter activity through Smad2's binding to gene promoter and TGF-β signaling promoted the stemness of colorectal cancer cells in an -dependent manner. This work identified a novel /TGF-β positive regulatory loop responsible for colorectal cancer stemness.
天冬酰胺连接的糖基化（ALG）成员在肿瘤发生过程中的作用已被广泛探索。然而，它们在结直肠癌进展中的作用仍存在混淆。在这里，我们通过在线数据集筛选了 12 种 ALG 的表达，发现 在结直肠癌组织中表达上调最为明显。我们发现， 敲低显著抑制了干性标志物、ALDH 活性和球体形成能力的表达。肿瘤发生分析表明， 敲低减弱了结直肠癌细胞的起始肿瘤能力和化疗耐药性。进一步的机制研究表明， 敲低通过减少 TGFBR2 糖基化抑制 TGF-β 信号转导活性，这对于 介导的结直肠癌细胞干性作用是必需的；相反，TGF-β 信号通过 Smad2 与 基因启动子结合激活 基因启动子活性，并通过 依赖性方式促进结直肠癌细胞的干性。这项工作确定了一个新的 /TGF-β 正反馈环，负责结直肠癌细胞干性。
