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

Junyi Wang,Xiaohong Xu,Yuhuan Ma,Leilei Hong,Junqing Ma,Lichan Yuan,Zhongyin Zhang

doi:10.1038/s41419-021-04448-3

Junyi Wang, Xiaohong Xu + Show 5 more

Open Access

https://doi.org/10.1038/s41419-021-04448-3

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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.

Highlights

Osteosarcoma (OS), as one of the common malignant bone tumors, is derived from osteoblasts and mainly affects adolescence and childhood [1, 2]
Expression of Triple functional domain (Trio) is elevated in OS In order to ascertain the role of Trio in OS, we firstly analyzed the data from the CCLE database and found that the mRNA level of Trio was relatively up-regulated in OS (Fig. 1A)
Trio was significantly elevated in OS cells compared with osteoblast cells both on the transcriptional level and the protein level (Fig. 1G–I)

Summary

Introduction

Osteosarcoma (OS), as one of the common malignant bone tumors, is derived from osteoblasts and mainly affects adolescence and childhood [1, 2]. It mostly occurs in the long bones, 6–10% in the craniofacial bones, causing jawbones lesions and facial deformities [1, 3]. Immunotherapy has proven to be a promising therapeutic strategy which intended to block molecular pathways associated with proliferation and metastasis of OS [7, 11]. Further research is needed for progressive strategies and novel treatment targets of OS

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