Abstract
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.
Highlights
Slit guidance ligand 2 (SLIT2) binds to roundaboutOsteosarcoma (OS) is the most common type of primary malignant bone tumor[1]
These results indicated that ROBO1 and SLIT2 were both upregulated in OS
IHC and TUNEL assay revealed a decreased expression of the proliferation marker Ki67 and an increased rate of apoptosis in the ROBO1-knockdown xenografts (Fig. 3e). These results indicated that SLIT2/ROBO1 axis promotes the proliferation of OS cells and inhibits their apoptosis
Summary
Slit guidance ligand 2 (SLIT2) binds to roundabout. Osteosarcoma (OS) is the most common type of primary malignant bone tumor[1]. It typically occurs in adolescents, with a second peak of incidence in the elderly[1]. Despite advances in chemotherapy and surgery over the guidance receptor 1 (ROBO1) and plays important roles in various physiological and pathological conditions, such as axon guidance, organ development, and pro-angiogenic function[3,4,5]. A better understanding of the molecular mechan- variety of tumors[6,7,8,9,10,11,12,13,14,15,16,17].
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