Open Access

GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1

  • Authors:
    • Zhi-Yun Yu
    • Hong-Jiang Li
    • Meng Wang
    • Wen-Zheng Luo
    • Ya-Ke Xue
  • View Affiliations

  • Published online on: July 27, 2022     https://doi.org/10.3892/ijo.2022.5399
  • Article Number: 109
  • Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer cells rewire their metabolism to meet the demands of growth and survival and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. However, the respective mechanisms remain elusive and the contribution of aberrant lipid metabolism to the malignant phenotypes of glioma are unclear. The present study demonstrated that glial‑derived neurotrophic factor (GDNF) is highly expressed in glioma and associated with poor clinical outcomes. In addition, there was a significant correlation between GDNF/rearranged during transfection (RET)/ERK signaling and sterol regulatory element‑binding protein‑1 (SREBP‑1) expression in glioma cells. Pharmacological or genetic inhibition of GDNF‑induced RET/ERK activity downregulated SREBP‑1 expression and SREBP‑1‑mediated transcription of lipogenic genes. Additionally, GDNF regulated SREBP‑1 activity by promoting hypoxia‑inducible factor‑1α (HIF‑1α) mediated glucose absorption and hexosamine biosynthetic pathway mediated SREBP cleavage‑activating protein N‑glycosylation. In addition, the inhibition of SREBP‑1 reduced the in vitro GDNF‑induced glioma cell proliferation. The results elucidated the complex relationship between GDNF/RET/ERK signaling and dysregulated glycolipid‑metabolism, which shows great potential to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.

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September-2022
Volume 61 Issue 3

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Copy and paste a formatted citation
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Spandidos Publications style
Yu Z, Li H, Wang M, Luo W and Xue Y: GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1. Int J Oncol 61: 109, 2022
APA
Yu, Z., Li, H., Wang, M., Luo, W., & Xue, Y. (2022). GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1. International Journal of Oncology, 61, 109. https://doi.org/10.3892/ijo.2022.5399
MLA
Yu, Z., Li, H., Wang, M., Luo, W., Xue, Y."GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1". International Journal of Oncology 61.3 (2022): 109.
Chicago
Yu, Z., Li, H., Wang, M., Luo, W., Xue, Y."GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1". International Journal of Oncology 61, no. 3 (2022): 109. https://doi.org/10.3892/ijo.2022.5399