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.

Cell Death & Disease
|March 11, 2018
PubMed

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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