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

Biochem Biophys Res Commun. 2022 Oct 30;627:91-96. doi: 10.1016/j.bbrc.2022.06.002. Epub 2022 Jun 7.

Abstract

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.

Keywords: Gastric cancer; LGR5; Progression; Rspondin-1.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplastic Stem Cells / pathology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Stomach Neoplasms* / pathology
  • Thrombospondins / metabolism*
  • Wnt Signaling Pathway

Substances

  • LGR5 protein, human
  • Receptors, G-Protein-Coupled
  • Thrombospondins