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Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
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Published on: January 22, 2018

Tumor metaboception: local PGE2 signals global decline

Ming-Zhu Jin1, Hao-Ran Dang2, Wei-Lin Jin2

  • 1Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200017, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200017, PR China.

Trends in Molecular Medicine
|August 13, 2026
PubMed

Insights

Cancer cachexia involves local signals, not just circulating factors. Liver kinase B1 (Lkb1)-mutant lung tumors release prostaglandin E2, causing anorexia and wasting via vagal neurons.

Area of Science:

  • Oncology
  • Neuroscience
  • Metabolism

Background:

  • Cancer cachexia is a complex syndrome characterized by involuntary weight loss.
  • Previous research suggested circulating factors mediate cachexia, but local mechanisms remain under investigation.

Purpose of the Study:

  • To investigate the role of local signaling in cancer cachexia, specifically in liver kinase B1 (Lkb1)-mutant lung tumors.
  • To identify the molecular mediators and neural pathways involved in Lkb1-mutant lung tumor-induced cachexia.

Main Methods:

  • Utilized a mouse model of Lkb1-mutant lung tumors.
  • Investigated the effects of prostaglandin E2 (PGE2) on vagal nerve activity and feeding behavior.
  • Assessed the impact of fat intake on cachexia progression.

Main Results:

  • Demonstrated that local prostaglandin E2 (PGE2) produced by Lkb1-mutant lung tumors directly activates vagal neurons.
  • Showed that this activation drives anorexia and contributes to systemic wasting.
  • Found that fat intake accelerates the wasting process in this model.

Conclusions:

  • Local PGE2 signaling from Lkb1-mutant lung tumors is a key driver of cancer cachexia.
  • Introduced the concept of 'metaboception' – neural sensing of local metabolic signals.
  • Suggests that targeting local signaling pathways, like PGE2-vagal neuron interactions, may offer novel therapeutic strategies for cancer cachexia.
Keywords:
LKB1/STK11cancer cachexiacancer neurosciencemetaboceptionprostaglandin E2vagus nerve

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