Suppression of cancer stemness by upregulating Ligand-of-Numb protein X1 in colorectal carcinoma.
Suppression of cancer stemness by upregulating Ligand-of-Numb protein X1 in colorectal carcinoma.
复制标题
通过上调结直肠癌中的 Ligand-of-Numb 蛋白 X1 来抑制癌症干细胞
DOI：
10.1371/journal.pone.0188665
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Yin W
中科院分区：
文献类型：
--
作者：
Ma L;Wang L;Shan Y;Nafees M;Ihab E;Zhang R;Wang F;Yin W
肿瘤干细胞样细胞（Cancer stem-like cells，CSCs）在结直肠癌（colorectal carcinoma，CRC）的发生、复发和转移中起重要作用。因此，鉴定结直肠CSC调节剂可以为CRC提供有希望的靶点。Numb配体蛋白X1（LNX 1）是一种E3泛素连接酶，介导Numb的泛素化和降解。尽管一些研究表明LNX 1可能是癌症疾病的潜在抑制因子，但LNX 1在介导癌症干性中的功能仍然知之甚少。在这项研究中，LNX 1被鉴定为CRC中癌症干细胞性的负调节因子，其在结肠球或侧群（SP）细胞中下调。此外，柯萨奇病毒和腺病毒受体（CXADR）被发现是一个关键的下游介质的癌症干细胞调节LNX 1。有趣的是，抗乳腺癌药物他莫昔芬被发现是LNX 1的激动剂，并抑制CRC中的癌症干细胞。本研究为LNX 1信号通路在调节结肠癌细胞干细胞性中发挥重要作用提供了证据。
Cancer stem-like cells (CSCs) have been reported to play major roles in tumorigenesis, tumor relapse, and metastasis after therapy against colorectal carcinoma (CRC). Therefore, identification of colorectal CSC regulators could provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3 ubiquitin ligase which mediates the ubiquitination and degradation of Numb. Although several studies indicate LNX1 could be a potential suppressor of cancer diseases, the functions of LNX1 in mediating cancer stemness remain poorly understood. In this study, LNX1 was identified as a negative regulator of cancer stemness in CRC, which was downregulated in colonospheres or side population (SP) cells. Furthermore, the coxsackievirus and adenovirus receptor (CXADR) was found to be one critical downstream mediator of cancer stemness regulated by LNX1. Interestingly, the anti-breast cancer drug tamoxifen was found to be an agonist of LNX1 and suppress cancer stemness in CRC. In sum, this study provided the evidences that LNX1 signaling plays important roles in regulating the stemness of colon cancer cells.
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影响因子：
2.9
作者：
Albini A;Bruno A;Gallo C;Pajardi G;Noonan DM;Dallaglio K
通讯作者：
Dallaglio K
影响因子：
2.5
作者：
Dean, Michael
通讯作者：
Dean, Michael
影响因子：
4.6
作者：
Kawada M;Inoue H;Kajikawa M;Sugiura M;Sakamoto S;Urano S;Karasawa C;Usami I;Futakuchi M;Masuda T
通讯作者：
Masuda T
DOI：
10.1016/j.biocel.2005.02.028
发表时间：
2005-11-01
影响因子：
4
作者：
Chen, JX;Xu, J;Lu, YC
通讯作者：
Lu, YC
影响因子：
4.2
作者：
Choi, Ji Eun;Bae, Jun Sang;Moon, Woo Sung
通讯作者：
Moon, Woo Sung