NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer Metastasis Article Swipe
Huafeng Fu
,
Jie Zhang
,
Hengxing Chen
,
Haobin Hou
,
Huanjie Chen
,
Rongman Xie
,
Yanlei Chen
,
Jian Zhang
,
Dehua Liu
,
Leping Yan
,
Rui L. Reis
,
Joaquím M. Oliveira
,
Yulong He
,
Li Zhong
,
Qinbo Cai
,
Dongjie Yang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202503233
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202503233
Metabolic reprogramming driven by oncogenes plays a critical role in promoting and sustaining multiple steps of gastric cancer metastasis. However, the key metabolic driver of metastasis that can lead to the development of targeted therapies for preventing and treating metastatic gastric cancer remains elusive. Here, it is identified that the transmembrane guanylate cyclase, natriuretic peptide receptor 1 (NPR1), promoted gastric cancer lymph node metastasis by activating lipid droplet lipolysis and enhancing mitochondrial oxidative phosphorylation (OXPHOS). Clinical analysis reveals that elevated NPR1 protein level is correlated with increased lymph node metastasis and shorter patient survival. Functionally, NPR1 induced lipolysis of stored lipid droplets, releasing bioavailable fatty acids that are imported into mitochondria to upregulate OXPHOS, thus fueling the energy required for the metastasis of gastric cancer cells. Mechanistically, NPR1 activates protein kinase cGMP‐dependent 1 (PRKG1 or PKG), which directly bound to and activated hormone‐sensitive lipase (HSL) by phosphorylation at residues Ser 855 and Ser 951 , thereby increasing lipolysis. Furthermore, targeted delivery of NPR1 siRNA using engineered exosome mimetics effectively suppressed gastric cancer metastasis. Taken together, these findings elucidate the NPR1‐driven metabolic mechanism underlying gastric cancer metastasis and suggest NPR1 as a promising therapeutic target for patients with metastatic gastric cancer.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/advs.202503233
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202503233
- OA Status
- gold
- Cited By
- 4
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411491381
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411491381Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/advs.202503233Digital Object Identifier
- Title
-
NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer MetastasisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-20Full publication date if available
- Authors
-
Huafeng Fu, Jie Zhang, Hengxing Chen, Haobin Hou, Huanjie Chen, Rongman Xie, Yanlei Chen, Jian Zhang, Dehua Liu, Leping Yan, Rui L. Reis, Joaquím M. Oliveira, Yulong He, Li Zhong, Qinbo Cai, Dongjie YangList of authors in order
- Landing page
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https://doi.org/10.1002/advs.202503233Publisher landing page
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202503233Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202503233Direct OA link when available
- Concepts
-
Lipolysis, Metastasis, Oxidative phosphorylation, Cancer research, Cancer, Cancer cell, Chemistry, Biology, Medicine, Internal medicine, Biochemistry, Adipose tissueTop concepts (fields/topics) attached by OpenAlex
- Cited by
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4Total citation count in OpenAlex
- Citations by year (recent)
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2025: 4Per-year citation counts (last 5 years)
- References (count)
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71Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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