Wu Jinxia, Du Wenqi, Wang Xiucun, Wei Lulu, Pan Yaojie, Wu Xiaojin, Zhang Jinling, Pei Dongsheng
Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Lett. 2018 Apr;15(4):5352-5358. doi: 10.3892/ol.2018.7987. Epub 2018 Feb 7.
Ras-related protein (Rap)2a and Rap2b are members of the GTP-binding protein family, and serve an important function in tumor progression. However, the associations between Rap2c and cancer cell functions have not yet been reported. Osteosarcoma is a type of bone cancer; its high degree of invasion is considered to be a major treatment challenge. The present study first investigated the biological role of Rap2c in human osteosarcoma cells and investigated the underlying mechanism of Rap2c on osteosarcoma cell migration and invasion. The results of the present study demonstrated that Rap2c overexpression promoted the migratory and invasive ability of cancer cells, and increased the activity of matrix metalloproteinase-2 (MMP2). Correspondingly, the knockdown of Rap2c inhibited tumor cell migration and invasion, whereas alterations to Rap2c had no effect on osteosarcoma cell proliferation or rate of apoptosis. Furthermore, Rap2c overexpression may decrease the protein level of tissue inhibitor of metalloproteinases 2 and increase the phosphorylation level of protein kinase B (Akt). Collectively, these results indicated that Rap2c has a key function in tumor migration and invasion, and the Akt signaling pathway may be involved in Rap2c-induced MMP2 expression.
Ras相关蛋白（Rap）2a和Rap2b是GTP结合蛋白家族的成员，在肿瘤进展中发挥重要作用。然而，Rap2c与癌细胞功能之间的关联尚未见报道。骨肉瘤是一种骨癌；其高度侵袭性被认为是主要的治疗挑战。本研究首次探讨了Rap2c在人骨肉瘤细胞中的生物学作用，并研究了Rap2c影响骨肉瘤细胞迁移和侵袭的潜在机制。本研究结果表明，Rap2c过表达促进了癌细胞的迁移和侵袭能力，并增加了基质金属蛋白酶-2（MMP2）的活性。相应地，敲低Rap2c可抑制肿瘤细胞的迁移和侵袭，而Rap2c的改变对骨肉瘤细胞增殖或凋亡率无影响。此外，Rap2c过表达可能降低金属蛋白酶组织抑制剂2的蛋白水平，并增加蛋白激酶B（Akt）的磷酸化水平。总体而言，这些结果表明Rap2c在肿瘤迁移和侵袭中起关键作用，且Akt信号通路可能参与Rap2c诱导的MMP2表达。
