SLIT2/ROBO1 axis contributes to the Warburg effect in osteosarcoma through activation of SRC/ERK/c-MYC/PFKFB2 pathway

• DOI: 10.1038/s41419-018-0419-y
• Publication Date: 2018-03-09T11:06:33Z
• Authors: Shu-Jie Zhao; Yi-Fei Shen; Qing Li; Yun-Jie He; Yun-Kun Zhang; Li-Peng Hu; Yu-Qing Jiang; Nan-Wei Xu; Yu-Ji Wang; Jun Li; Ya-Hui Wang; Fei Liu; Rong Zhang; Guo-Yong Yin; Jin-Hai Tang; Dong Zhou; Zhi-Gang Zhang
• Keywords: Male; Mice, Inbred BALB C; Osteosarcoma; 0303 health sciences; Phosphofructokinase-2; Roundabout Proteins; Mice, Nude; Nerve Tissue Proteins; Article; Oxidative Phosphorylation; 3. Good health; Proto-Oncogene Proteins c-myc; Mice; 03 medical and health sciences; src-Family Kinases; Animals; Heterografts; Humans; Intercellular Signaling Peptides and Proteins; Receptors, Immunologic; Glycolysis; Signal Transduction

AbstractCellular 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.