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Rho-GEF Trio 通过 Rac1 和 RhoA 调节骨肉瘤的进展和成骨分化。

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

机构信息

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, 210029, Nanjing, China.

Nanjing Foreign Language School, 210008, Nanjing, Jiangsu, China.

出版信息

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.

摘要

骨肉瘤(OS)是最常见的原发性骨肿瘤。其高死亡率和转移率严重威胁着人类的健康。目前,治疗已经达到了一个瓶颈,因此我们急需探索新的治疗方向。在本文中,我们发现 Trio 在骨肉瘤中的表达水平明显高于正常组织,并促进了骨肉瘤细胞的增殖、迁移和侵袭。此外,Trio 在体外抑制了骨肉瘤细胞的成骨分化,并加速了骨肉瘤在体内的生长。鉴于 Trio 含有两个 GEF 结构域,这些结构域已被报道为 RhoGTPases 的调节剂,我们进一步发现 Trio 可以通过激活 RhoGTPases 来调节骨肉瘤的进展和成骨分化。总之,我们所有的初步结果表明,Trio 可能是骨肉瘤的一个潜在的治疗靶点和预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f979/8664940/03757311a26a/41419_2021_4448_Fig1_HTML.jpg

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