Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
Department of Orthopedics, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, 213003, Jiangsu, China.
Cell Death Dis. 2018 Mar 9;9(3):390. doi: 10.1038/s41419-018-0419-y.
Cellular metabolic reprogramming is the main characteristic of cancer cells and identification of targets using this metabolic pattern is extremely important to treat cancers, such as osteosarcoma (OS). In this study, SLIT2 and ROBO1 were upregulated in OS, and higher expression of ROBO1 was associated with worse overall survival rate. Furthermore, in vitro and in vivo experiments demonstrated that the SLIT2/ROBO1 axis promotes proliferation, inhibits apoptosis, and contributes to the Warburg effect in OS cells. Mechanistically, the SLIT2/ROBO1 axis exerted cancer-promoting effects on OS via activation of the SRC/ERK/c-MYC/PFKFB2 pathway. Taken together, the findings reveal a previously unappreciated function of SLIT2/ROBO1 signaling in OS, which is intertwined with metabolic alterations that promote cancer progression. Targeting the SLIT2/ROBO1 axis may be a potential therapeutic approach for patients with OS.
细胞代谢重编程是癌细胞的主要特征，利用这种代谢模式识别靶点对于治疗癌症（如骨肉瘤）极其重要。在本研究中，SLIT2 和 ROBO1 在骨肉瘤中上调，并且 ROBO1 的高表达与总体生存率降低相关。此外，体外和体内实验表明，SLIT2/ROBO1 轴促进骨肉瘤细胞的增殖、抑制凋亡，并有助于 Warburg 效应。在机制上，SLIT2/ROBO1 轴通过激活 SRC/ERK/c-MYC/PFKFB2 通路对骨肉瘤发挥致癌作用。总之，这些发现揭示了 SLIT2/ROBO1 信号在骨肉瘤中的一个以前未被认识到的功能，它与促进癌症进展的代谢改变交织在一起。靶向 SLIT2/ROBO1 轴可能是骨肉瘤患者的一种潜在治疗方法。
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