SPC24通过增强表皮生长因子受体/丝裂原活化蛋白激酶信号通路促进骨肉瘤进展。

SPC24 promotes osteosarcoma progression by increasing EGFR/MAPK signaling.

作者信息

Sheng Jun, Yin Mengchen, Sun Zhengwang, Kang Xia, Liu Da, Jiang Kai, Xu Jia, Zhao Feixing, Guo Qunfeng, Zheng Wei

机构信息

Department of Orthopedics, Chengdu Military General Hospital, Chengdu, Sichuan, China.

Department of Orthopedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Oncotarget. 2017 Oct 27;8(62):105276-105283. doi: 10.18632/oncotarget.22167. eCollection 2017 Dec 1.

In this study, we investigated the role of the spindle checkpoint protein SPC24 in osteosarcoma progression. SPC24 knockdown in 143B and U2OS osteosarcoma cells decreased cell growth, survival and invasiveness. The SPC24 knockdown cells also exhibited low EGFR, Ras and phospho-ERK levels and high E-cadherin levels, suggesting inhibition of EGFR/Ras/ERK signaling and epithelial-to-mesenchymal transitioning. Xenografted SPC24 knockdown osteosarcoma cells showed reduced tumor growth in nude mice with decreased EGFR and phospho-ERK levels and increased E-cadherin levels. By contrast, human osteosarcoma tissue samples showed high SPC24 and phospho-ERK levels and low E-cadherin levels. These results suggest SPC24 promotes osteosarcoma progression by increasing EGFR/Ras/ERK signaling.

在本研究中，我们调查了纺锤体检查点蛋白SPC24在骨肉瘤进展中的作用。在143B和U2OS骨肉瘤细胞中敲低SPC24可降低细胞生长、存活和侵袭能力。敲低SPC24的细胞还表现出低水平的表皮生长因子受体（EGFR）、Ras和磷酸化细胞外信号调节激酶（phospho-ERK）以及高水平的E-钙黏蛋白，提示EGFR/Ras/ERK信号传导受到抑制以及上皮-间质转化受到抑制。异种移植的敲低SPC24的骨肉瘤细胞在裸鼠中显示肿瘤生长减缓，伴有EGFR和磷酸化ERK水平降低以及E-钙黏蛋白水平升高。相比之下，人类骨肉瘤组织样本显示SPC24和磷酸化ERK水平较高，而E-钙黏蛋白水平较低。这些结果表明，SPC24通过增强EGFR/Ras/ERK信号传导促进骨肉瘤进展。