Leucine-rich repeat-containing G protein-coupled receptor 5 regulates epithelial cell phenotype and survival of hepatocellular carcinoma cells
Leucine-rich repeat-containing G protein-coupled receptor 5 regulates epithelial cell phenotype and survival of hepatocellular carcinoma cells
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DOI：
10.1016/j.yexcr.2012.10.011
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发表时间：
2013-02-01
影响因子：
3.7
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Fukuma, Mariko;Tanese, Keiji;Sakamoto, Michiie
富含亮氨酸重复序列的 G 蛋白偶联受体 5 (LGR5)，也称为 GPR49，是一种七跨膜受体，在小鼠肠隐窝和毛囊的干细胞中表达。 LGR5在某些类型的人类癌症中过度表达，是Wnt信号通路的靶基因之一。为了探索 LGR5 在癌细胞中的功能，建立了表达 FLAG 标记的 LGR5 的稳定肝细胞癌 (HCC) 细胞系。 LGR5 的过度表达导致细胞形状从扩展的扁平（间充质）表型变为圆形聚集（干细胞样）表型。与空载体转染的细胞相比，LGR5转染的细胞表现出更高的集落形成活性，并且对细胞毒性药物具有更强的抵抗力。 LGR5 的过度表达抑制细胞运动。 LGR5转染的细胞在免疫缺陷小鼠的肝脏中形成结节型肿瘤，而空载体转染的细胞则形成更具侵袭性的肿瘤。 LGR5的下调使HCC细胞的形态从聚集表型改变为延长的纺锤体表型，并且细胞运动性增加。这是第一项报告 LGR5 在 HCC 细胞生物学中的功能作用的研究，结果表明 LGR5 的异常表达可调节上皮细胞表型和存活。 (c) 2012 Elsevier Inc. 保留所有权利。
The leucine-rich repeat containing G protein-coupled receptor 5 (LGR5), also known as GPR49, is a seven-transmembrane receptor that is expressed in stem cells of the intestinal crypts and hair follicles of mice. LGR5 is overexpressed in some types of human cancer, and is one of the target genes of the Wnt signaling pathway. To explore the function of LGR5 in cancer cells, stable hepatocellular carcinoma (HCC) cell lines expressing FLAG-tagged LGR5 were established. Overexpression of LGR5 resulted in changes in cell shape from an extended flat (mesenchymal) phenotype to a round aggregated (stem cell-like) phenotype. Cells transfected with LGR5 showed higher colony forming activity, and were more resistant to a cytotoxic drug than cells transfected with empty vector. Overexpression of LGR5 inhibited cell motility. LGR5-transfected cells formed nodule type tumors in the livers of immunodeficient mice, whereas empty vector-transfected cells formed more invasive tumors. Down-regulation of LGR5 changed the morphology of HCC cells from the aggregated phenotype to an extended spindle phenotype, and cell motility was increased. This is the first study reporting the functional role of LGR5 in the biology of HCC cells, and the results suggest that aberrant expression of LGR5 regulates epithelial cell phenotype and survival. (c) 2012 Elsevier Inc. All rights reserved.