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.

Details

Title
SLIT2/ROBO1 axis contributes to the Warburg effect in osteosarcoma through activation of SRC/ERK/c-MYC/PFKFB2 pathway
Author
Shu-Jie Zhao 1 ; Yi-Fei, Shen 2 ; Li, Qing 3 ; Yun-Jie, He 4 ; Yun-Kun, Zhang 2 ; Li-Peng, Hu 3 ; Yu-Qing, Jiang 2 ; Nan-Wei, Xu 2 ; Yu-Ji, Wang 2 ; Li, Jun 3 ; Wang, Ya-Hui 3 ; Liu, Fei 5 ; Zhang, Rong 6 ; Guo-Yong, Yin 7 ; Jin-Hai, Tang 4 ; Zhou, Dong 2 ; Zhang, Zhi-Gang 3   VIAFID ORCID Logo 

1  Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Department of Orthopedics, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, Jiangsu, China 
2  Department of Orthopedics, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, Jiangsu, China 
3  State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 
4  Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China 
5  Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China 
6  Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai, China 
7  Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 
Pages
1-13
Publication year
2018
Publication date
Mar 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-018-0419-y
ProQuest document ID
2019458142
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.