Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
Biochem Biophys Res Commun. 2022 Oct 30;627:91-96. doi: 10.1016/j.bbrc.2022.06.002. Epub 2022 Jun 7.
Gastric cancer is a one of the most common malignant tumors with poor prognosis worldwide. Leucine-rich G-protein-coupled receptor 5 (LGR5) is determined as a modulator of Wnt signaling cascade and R-spondins are a family of secretory agonists in the Wnt signaling and act as ligands to interact with LGR5. However, the function of Rspondin-1 in GC remains obscure. Here, we identified the effect of Rspondin-1 on GC progression. Rspondin-1 and LGR5 were upregulated in clinical gastric cancer tissues. CCK-8 assay revealed that the viability of GC cells was reduced by Rspondin-1 depletion and enhanced by Rspondin-1 overexpression. The depletion of Rspondin-1 decreased while the overexpression of Rspondin-1 increased the numbers of colony formation and Edu-positive GC cells. The depletion of Rspondin-1 attenuated the invasion and migration ability of GC cells. Moreover, sphere formation assays revealed that the knockdown of Rspondin-1 reduced the stemness of GC cells. The expression of cancer stem cell markers, including Nanog, OCT3/4, and SOX2 were suppressed by Rspondin-1 depletion in GC cells. Rspondin-1 induced tumor growth of gastric cancer cells in vivo. Mechanically, the cell viability and invasion suppressed by the depletion of Rspondin-1 in GC cells were rescued by LGR5 overexpression. Besides, the overexpression of LGR5 reversed Rspondin-1 knockdown-inhibited Nanog and OCT3/4 expression. Consequently, we concluded that Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.
胃癌是全球最常见的恶性肿瘤之一，预后较差。富含亮氨酸的 G 蛋白偶联受体 5（LGR5）被确定为 Wnt 信号级联的调节剂，而 R 脊椎蛋白是 Wnt 信号中的一类分泌激动剂家族，作为配体与 LGR5 相互作用。然而，Rspondin-1 在 GC 中的功能仍不清楚。在这里，我们确定了 Rspondin-1 对 GC 进展的影响。Rspondin-1 和 LGR5 在临床胃癌组织中上调。CCK-8 测定表明，Rspondin-1 耗竭降低了 GC 细胞的活力，而过表达 Rspondin-1 则增强了 GC 细胞的活力。Rspondin-1 耗竭减少，而过表达 Rspondin-1 则增加了集落形成和 Edu 阳性 GC 细胞的数量。Rspondin-1 耗竭减弱了 GC 细胞的侵袭和迁移能力。此外，球体形成测定表明，Rspondin-1 的敲低降低了 GC 细胞的干性。Rspondin-1 耗竭下调了 GC 细胞中癌症干细胞标志物的表达，包括 Nanog、OCT3/4 和 SOX2。Rspondin-1 在体内诱导胃癌细胞的肿瘤生长。在机制上，Rspondin-1 耗竭在 GC 细胞中抑制细胞活力和侵袭，通过 LGR5 过表达得到挽救。此外，LGR5 的过表达逆转了 Rspondin-1 敲低抑制的 Nanog 和 OCT3/4 表达。因此，我们得出结论，Rspondin-1 通过 LGR5 促进胃癌的进展和干性。
