Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA

Cell Death Dis. 2021 Dec 11;12(12):1148. doi: 10.1038/s41419-021-04448-3.

Abstract

Osteosarcoma (OS) is the most common primary bone tumor. Its high mortality rate and metastasis rate seriously threaten human health. Currently, the treatment has reached a plateau, hence we urgently need to explore new therapeutic directions. In this paper, we found that Trio was highly expressed in osteosarcoma than normal tissues and promoted the proliferation, migration, and invasion of osteosarcoma cells. Furthermore, Trio inhibited osteosarcoma cells' osteogenic differentiation in vitro and accelerated the growth of osteosarcoma in vivo. Given Trio contains two GEF domains, which have been reported as the regulators of RhoGTPases, we further discovered that Trio could regulate osteosarcoma progression and osteogenic differentiation through activating RhoGTPases. In summary, all our preliminary results showed that Trio could be a potential target and prognostic marker of osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Guanine Nucleotide Exchange Factors* / genetics
  • Guanine Nucleotide Exchange Factors* / metabolism
  • Humans
  • Osteogenesis / genetics
  • Osteosarcoma* / genetics
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • rac1 GTP-Binding Protein* / genetics
  • rac1 GTP-Binding Protein* / metabolism
  • rhoA GTP-Binding Protein* / genetics
  • rhoA GTP-Binding Protein* / metabolism

Substances

  • Guanine Nucleotide Exchange Factors
  • RAC1 protein, human
  • RHOA protein, human
  • Protein Serine-Threonine Kinases
  • TRIO protein, human
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein