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首页> 外文期刊>British Journal of Cancer >Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?
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Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?

机译：针对大肠癌中的LGR5：治疗性金还是可塑性？

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Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-catenin signalling and is a marker of normal stem cells in several tissues, including the intestine. Consistent with stem cell potential, single isolated LGR5~(+)cells from the gut generate self-organising crypt/villus structures in vitro termed organoids or ‘mini-guts’, which accurately model the parent tissue. The well characterised deregulation of Wnt/β-catenin signalling that occurs during the adenoma-carcinoma sequence in colorectal cancer (CRC) renders LGR5 an interesting therapeutic target. Furthermore, recent studies demonstrating that CRC tumours contain LGR5~(+)subsets and retain a degree of normal tissue architecture has heightened translational interest. Such reports fuel hope that specific subpopulations or molecules within a tumour may be therapeutically targeted to prevent relapse and induce long-term remissions. Despite these observations, many studies within this field have produced conflicting and confusing results with no clear consensus on the therapeutic value of LGR5. This review will recap the various oncogenic and tumour suppressive roles that have been described for the LGR5 molecule in CRC. It will further highlight recent studies indicating the plasticity or redundancy of LGR5~(+)cells in intestinal cancer progression and assess the overall merit of therapeutically targeting LGR5 in CRC.
机译：富含亮氨酸的重复序列包含的G蛋白偶联受体（LGR5或GPR49）增强了规范的Wnt /β-catenin信号传导，并且是包括肠道在内的多种组织中正常干细胞的标志物。与干细胞潜能一致，从肠道中分离出的单个LGR5〜（+）细胞可在体外产生自组织的隐窝/绒毛结构，称为类器官或“小肠”，可精确模拟母体组织。在结直肠癌（CRC）的腺瘤-癌序列中发生的Wnt /β-catenin信号失调的特征充分，使LGR5成为有趣的治疗靶标。此外，最近的研究表明，CRC肿瘤包含LGR5〜（+）亚集并保留一定程度的正常组织结构，这引起了翻译的兴趣。此类报道使人们希望将肿瘤内的特定亚群或分子作为治疗靶点，以预防复发并诱导长期缓解。尽管有这些观察结果，该领域内的许多研究仍产生了令人困惑的结果，但对LGR5的治疗价值尚无明确共识。这篇综述将概述CRC中LGR5分子所描述的各种致癌和抑癌作用。它将进一步强调最近的研究，这些研究表明LGR5〜（+）细胞在肠道癌进展中具有可塑性或冗余性，并评估在CRC中靶向治疗LGR5的总体优势。

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