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Published on: November 29, 2016
SLIT2/ROBO1 axis contributes to the Warburg effect in osteosarcoma through activation of SRC/ERK/c-MYC/PFKFB2 pathway
Shu-Jie Zhao1,2, Yi-Fei Shen2, Qing Li3
1Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
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.
Insights
This study reveals that the SLIT2/ROBO1 signaling pathway promotes osteosarcoma (OS) progression by altering cell metabolism. Targeting this axis offers a potential therapeutic strategy for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Cellular metabolic reprogramming is a hallmark of cancer, crucial for identifying therapeutic targets in osteosarcoma (OS).
- The SLIT2/ROBO1 signaling pathway's role in OS and its metabolic implications remain largely unexplored.
Purpose of the Study:
- To investigate the role of the SLIT2/ROBO1 axis in osteosarcoma (OS) progression and its association with cellular metabolism.
- To elucidate the underlying molecular mechanisms driving OS by the SLIT2/ROBO1 axis.
Main Methods:
- Analysis of SLIT2 and ROBO1 expression in OS tissues.
- In vitro and in vivo experiments to assess the functional impact of the SLIT2/ROBO1 axis on OS cell proliferation, apoptosis, and metabolism.
- Investigation of the SRC/ERK/c-MYC/PFKFB2 signaling pathway.
Main Results:
- SLIT2 and ROBO1 were found to be upregulated in OS, with higher ROBO1 expression correlating with poorer survival.
- The SLIT2/ROBO1 axis was demonstrated to enhance OS cell proliferation, suppress apoptosis, and promote the Warburg effect.
- Activation of the SRC/ERK/c-MYC/PFKFB2 pathway was identified as the mechanism by which the SLIT2/ROBO1 axis promotes cancer progression in OS.
Conclusions:
- The SLIT2/ROBO1 signaling pathway plays a significant role in osteosarcoma progression through metabolic alterations.
- Targeting the SLIT2/ROBO1 axis presents a promising therapeutic avenue for osteosarcoma treatment.
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