LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer.
LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer.
复制标题
LGR5 促进宫颈癌干细胞特性和化疗耐药性
DOI：
10.1038/cddis.2017.393
复制
发表时间：
2017-09-07
影响因子：
9
通讯作者：
Zheng PS
中科院分区：
文献类型：
--
作者：
Cao HZ;Liu XF;Yang WT;Chen Q;Zheng PS
癌症干细胞（CSCs）也称为肿瘤起始细胞，有助于人类癌症的肿瘤发生、对放化疗的抵抗和复发，这表明靶向CSCs可能代表潜在的治疗策略。最近发现富含亮氨酸重复序列的G蛋白偶联受体5（LGR 5）是结直肠CSC的真正标志物。我们先前的研究表明LGR 5通过激活Wnt/β-catenin通路在宫颈癌中起肿瘤促进剂的作用。然而，关于LGR 5对宫颈CSC的功能或贡献知之甚少。在这里，我们使用过表达载体或短发夹RNA在宫颈癌细胞系中调节LGR 5的表达。我们证明，宫颈癌细胞中LGR 5表达升高增加了肿瘤球形成效率;赋予顺铂治疗的化疗耐药性;增强了细胞迁移、侵袭和克隆形成;并在体外升高了干细胞相关转录因子的水平。此外，与LGR 5 −细胞不同，调制的LGR 5+细胞在体内具有高度致瘤性。此外，调节的LGR 5+细胞可以在体外和体内产生LGR 5+和LGR 5 −细胞，从而建立细胞层次。最后，我们发现LGR 5诱导的肿瘤球形成效率的增加可以通过抑制或激活宫颈癌细胞中的Wnt/β-catenin通路来调节。总之，这些结果表明LGR 5通过促进宫颈CSC性状而具有重要的致癌作用，并且可能代表潜在的临床靶点。
Cancer stem cells (CSCs), also known as tumor-initiating cells, contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) has recently been found to be a bona fide marker of colorectal CSCs. Our previous study showed that LGR5 functions as a tumor promoter in cervical cancer by activating the Wnt/β-catenin pathway. However, very little is known about the function or contribution of LGR5 to cervical CSCs. Here, we have modulated the expression of LGR5 using an overexpression vector or short hairpin RNA in cervical cancer cell lines. We demonstrated that elevated LGR5 expression in cervical cancer cells increased tumorsphere-forming efficiency; conferred chemoresistance to cisplatin treatment; augmented cell migration, invasion and clonogenicity; and elevated the levels of stem cell-related transcription factors in vitro. Furthermore, modulated LGR5+ cells, unlike LGR5− cells, were highly tumorigenic in vivo. In addition, the modulated LGR5+ cells could give rise to both LGR5+ and LGR5− cells in vitro and in vivo, thereby establishing a cellular hierarchy. Finally, we found that the increased tumorsphere-forming efficiency induced by LGR5 could be regulated through the inhibition or activation of the Wnt/β-catenin pathway in cervical cancer cells. Taken together, these results indicate that LGR5 has a vital oncogenic role by promoting cervical CSC traits and may represent a potential clinical target.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.7
作者：
Scannell CA;Pedersen EA;Mosher JT;Krook MA;Nicholls LA;Wilky BA;Loeb DM;Lawlor ER
通讯作者：
Lawlor ER
影响因子：
4.7
作者：
Hirsch, Daniela;Barker, Nick;Gaiser, Timo
通讯作者：
Gaiser, Timo
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
9
作者：
通讯作者：
--