Chen Ming-Wei, Wu Xue-Jian
1 Orthopedics department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan province, China.
Technol Cancer Res Treat. 2018 Jan 1;17:1533033818811143. doi: 10.1177/1533033818811143.
Osteosarcoma is a highly malignant bone tumor. However, due to the high complexity of the occurrence and metastasis of osteosarcoma, the exact mechanism promoting its development and progression remains to be elucidated. This study highlights the causal link between solute carrier family 25 member 22 (SLC25A22) and the development, progression, and metastasis of osteosarcoma. SLC25A22 is upregulated in human osteosarcoma and predicts a poor prognosis. The upregulation of SLC25A22 in osteosarcoma tissues was significantly associated with cell proliferation, invasion, and metastasis. Studies of functional gain (overexpression) and loss (knockdown) showed that SLC25A22 significantly increases the ability of osteosarcoma cells to proliferate, as well as invade and metastasize in vitro. At the same time, the expression of SLC25A22 promoted the progression of the cellcycle of osteosarcoma cell lines and inhibited the apoptosis of osteosarcoma cells. Analysis using a mouse xenograft model showed that xenografts of SLC25A22 stable overexpressing osteosarcoma cells had a significant increase in tumor volume and weight compared to the control group. Lung metastasis models in mice showed that expression of SLC25A22 promoted lung metastasis of osteosarcoma in vivo. Furthermore, SLC25A22 inhibited phosphatase and tensin homolog expression and increased phosphorylation of protein kinase b (Akt) and Focal Adhesion Kinase (FAK) in the phosphatase and tensin homolog signaling pathway. In summary, SLC25A22 is highly expressed in osteosarcoma, promoting osteosarcoma cell proliferation and invasion by inhibiting the phosphatase and tensin homolog signaling pathway.
骨肉瘤是一种高度恶性的骨肿瘤。然而,由于骨肉瘤发生和转移的高度复杂性,其促进发展和进展的确切机制仍有待阐明。本研究强调了溶质载体家族25成员22(SLC25A22)与骨肉瘤的发生、发展和转移之间的因果关系。SLC25A22在人类骨肉瘤中上调,并预示预后不良。骨肉瘤组织中SLC25A22的上调与细胞增殖、侵袭和转移显著相关。功能获得(过表达)和缺失(敲低)研究表明,SLC25A22显著增加骨肉瘤细胞的增殖能力,以及在体外的侵袭和转移能力。同时,SLC25A22的表达促进了骨肉瘤细胞系细胞周期的进展,并抑制了骨肉瘤细胞的凋亡。使用小鼠异种移植模型分析表明,与对照组相比,SLC25A22稳定过表达的骨肉瘤细胞异种移植瘤的体积和重量显著增加。小鼠肺转移模型表明,SLC25A22的表达促进了骨肉瘤在体内的肺转移。此外,SLC25A22抑制磷酸酶和张力蛋白同源物的表达,并增加了磷酸酶和张力蛋白同源物信号通路中蛋白激酶b(Akt)和粘着斑激酶(FAK)的磷酸化。总之,SLC25A22在骨肉瘤中高表达,通过抑制磷酸酶和张力蛋白同源物信号通路促进骨肉瘤细胞增殖和侵袭。