LGR4 promotes tumorigenesis by activating TGF-β1/Smad signaling pathway in multiple myeloma

Cell Signal. 2023 Oct:110:110814. doi: 10.1016/j.cellsig.2023.110814. Epub 2023 Jul 18.

Abstract

Multiple myeloma (MM) is a common hematologic malignancy that remains incurable. Although accumulating evidence suggests that the leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays a biological function in a variety of cancers, its biological function and molecular mechanisms in MM are unclear. In the present study, we found that LGR4 was significantly upregulated in MM tissues and cells. In vitro and in vivo experiments showed that knockdown of LGR4 significantly inhibited proliferation of MM cells, promoted apoptosis and arrested cell cycle in G1. Overexpression showed the opposite effect. Mechanistic studies revealed that LGR4 could interact with TGF-β1 and regulate TGF-β1 expression, thereby activating the TGF-β1/Smad signaling pathway and promoting MM progression. LGR4 may be a potential new target for MM diagnosis and treatment.

Keywords: Apoptosis; LGR4; Multiple myeloma; Proliferation; TGF-β1/Smad.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • Humans
  • Multiple Myeloma* / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1* / metabolism

Substances

  • LGR4 protein, human
  • Receptors, G-Protein-Coupled
  • Transforming Growth Factor beta1
  • Smad Proteins