AGR2 is a target of canonical Wnt/β-catenin signaling and is important for sternness maintenance in colorectal cancer stem cells
AGR2 is a target of canonical Wnt/β-catenin signaling and is important for sternness maintenance in colorectal cancer stem cells
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DOI：
10.1016/j.bbrc.2019.05.154
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发表时间：
2019-08-06
影响因子：
3.1
通讯作者：
Kwon, Sang-Mo
中科院分区：
文献类型：
--
作者：
Lamichane, Babita Dahal;Jung, Seok Yun;Kwon, Sang-Mo
结直肠癌是癌症相关死亡的主要原因之一。由于目前的治疗方案后复发，正在研究癌症干细胞（CSC）以靶向这个小的肿瘤起始群体。前梯度2（AGR 2）是一种二硫键异构酶蛋白，是众所周知的在各种肿瘤组织（包括结肠癌）中过表达的原癌基因/转移癌基因。我们发现AGR 2是一种新的干细胞标志物，在结肠CSC中受经典Wnt/β-连环蛋白通路调节。AGR 2与表面干细胞标志物在球形培养物中高度共表达。沉默AGR 2导致球体形成能力降低和干细胞标记物表达下调，而AGR 2过表达则产生相反的效果。此外，β-连环蛋白和AGR 2高表达的患者的总体生存率低于低表达的患者。总之，我们的研究描述了AGR 2作为干细胞标志物的新作用，该干细胞标志物在结直肠癌中受到经典Wnt/β-连环蛋白信号的高度调节。(C)2019爱思唯尔公司All rights reserved.
Colorectal cancer is one of the leading causes of cancer-related deaths. Due to relapse after current therapy regimens, cancer stem cells (CSCs) are being studied to target this small tumor-initiating population. Anterior gradient 2 (AGR2), a disulfide isomerase protein, is a well-known pro-oncogenic/metastatic oncogene overexpressed in various tumor tissues, including colon cancer. We found that AGR2 was a novel stem cell marker that was regulated by the canonical Wnt/beta-catenin pathway in colon CSCs. AGR2 was highly co-expressed with surface stem cell markers in spheroidal culture. Silencing of AGR2 resulted in decreased sphere-forming ability and down-regulated expression of stem cell markers, whereas the opposite effects were seen with AGR2 overexpression. Moreover, patients with high beta-catenin and AGR2 expression showed lower overall survival than those with low expression. In conclusion, our study describes a novel role for AGR2 as a stem cell marker that is highly regulated by canonical Wnt/beta-catenin signaling in colorectal cancer. (C) 2019 Elsevier Inc. All rights reserved.