Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2022-10, Vol.627, p.91-96
Main Authors: Wang, Chuang, Gao, Yunhe, Liang, Wenquan, Lu, Yixun, Zhang, KeCheng, Wu, Di, Zhuang, ZiWei, Li, Kai, Qiao, Zhi, Xi, Hongqing, Chen, Lin
Format: Article
Language:English
Subjects:
Gastric cancer
LGR5
Progression
Rspondin-1
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Summary: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. •Rspondin-1 and LGR5 are upregulated in clinical gastric cancer tissues.•Rspondin-1 contributes to proliferation of gastric cancer cells in vitro.•Rspondin-1 promotes migration and invasion of gastric cancer cells in vitro.•Rspondin-1 enhances cancer stem cell properties of gastric cancer cells in vitro.•Rspondin-1 induces tumor growth of gastric cancer cells in vivo•Rspondin-1 contributes to progression of gastric cancer by LGR5.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2022.06.002