Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI

Abhishek Tyagi, Shih-Ying Wu, Jee-Won Kim, Ravindra Pramod Deshpande, Kerui Wu, Eleanor C. Smith, Giuseppe L. Banna and Kounosuke Watabe ()
Additional contact information
Abhishek Tyagi: Wake Forest University School of Medicine
Shih-Ying Wu: Wake Forest University School of Medicine
Jee-Won Kim: Wake Forest University School of Medicine
Ravindra Pramod Deshpande: Wake Forest University School of Medicine
Kerui Wu: Joint School of Nanoscience & Nanoengineering
Eleanor C. Smith: Wake Forest University School of Medicine
Giuseppe L. Banna: University of Portsmouth
Kounosuke Watabe: Wake Forest University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Obesity is a known risk factor for many cancers, yet recent studies reveal a paradoxical association between low body mass index (BMI) and increased brain metastasis in lung cancer—referred to as the “obesity paradox,” with unclear molecular mechanism(s). Here, we show a significantly higher incidence of brain metastasis in low-BMI lung cancer patients compared to those with high-BMI or other cancer brain metastasis in a pan-analysis of 7628 patients. Mechanistically, low BMI activates ghrelin-GHSR signaling, increasing neuronal neuropeptide Y (NPY) secretion, which promotes tumor metabolic reprogramming via NPY-Y5R, facilitating brain colonization. Elevated plasma ghrelin levels in cancer-free low-BMI subjects suggest its potential as a prognostic biomarker for predicting brain metastasis. Notably, targeting NPY-Y5R or reversing low BMI effectively suppresses brain metastasis, supporting its pro-metastatic role. These findings provide a strong rationale for developing targeted interventions to treat or prevent brain metastasis in lung cancer patients with low BMI.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60730-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60730-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60730-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().