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Hierarchical Disruption of the Tryptophan-Melatonin Axis Contributes to Glioma Progression Through AKT/ERK/STAT3

Bo Tan1, Suqiu Yao1, Shuangyin He1

  • 1Department of Neurosurgery, Guangyuan Central Hospital, Guangyuan, Sichuan, China.

Journal of Cellular and Molecular Medicine
|June 13, 2026
PubMed

Insights

The tryptophan-melatonin axis is disrupted in glioma, with reduced melatonin receptors (MTNR1A, MTNR1B) and enzymes (AANAT, ASMT) linked to poor prognosis. Restoring these factors inhibits glioma progression.

Area of Science:

  • Neuroscience
  • Oncology
  • Molecular Biology

Background:

  • Melatonin signaling regulates circadian and neuroendocrine functions.
  • The integrity of the tryptophan-melatonin axis during glioma progression is not well understood.

Purpose of the Study:

  • To investigate the hierarchical disruption of the tryptophan-melatonin axis in glioma.
  • To determine the impact of this disruption on glioma progression and downstream signaling.

Main Methods:

  • Integrated transcriptomic data (TCGA, CGGA, GTEx) for melatonin pathway genes.
  • Validated protein expression via immunohistochemistry.
  • Conducted gain- and loss-of-function studies in glioma cells.

Main Results:

  • Coordinated downregulation of AANAT, ASMT, MTNR1A, and MTNR1B with increasing glioma grade.
  • Reduced expression correlated with poor prognosis and was confirmed at the protein level.
  • Restoration of MTNR1A/ASMT suppressed proliferation, migration, and invasion, while promoting apoptosis.

Conclusions:

  • Hierarchical disruption of melatonin signaling is a key feature of glioma.
  • This disruption promotes malignant progression via AKT/ERK/STAT3 activation.
  • The tryptophan-melatonin axis holds therapeutic relevance for glioma.
Keywords:
ASMTMTNR1AAKT signallingERK pathwaySTAT3gliomamelatoninmolecular mechanismtumour progression

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