G-protein-coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1-mediated redox modulation
View abstract on PubMed
Summary
This summary is machine-generated.This study reveals G-protein-coupled estrogen receptor (GPER1) promotes gastric cancer peritoneal metastasis by affecting cell anoikis. Inhibiting GPER1-mediated NADK1 activity offers a potential therapeutic strategy.
Area Of Science
- Oncology
- Endocrinology
- Cell Biology
Background
- Adipose tissue is a key site for estrogen production via aromatase.
- Gastric cancer often involves adipocyte-rich peritoneal metastasis, with unclear mechanisms.
- Estrogen signaling pathways are implicated in various cancers.
Purpose Of The Study
- To investigate the role of G-protein-coupled estrogen receptor 1 (GPER1) in gastric cancer peritoneal metastasis.
- To elucidate the molecular mechanisms linking GPER1 to cancer cell survival and metastasis.
- To identify potential therapeutic targets for gastric cancer peritoneal metastasis.
Main Methods
- In vitro cell culture studies assessing anoikis and cell behavior.
- Genetic manipulation of GPER1 (overexpression and knockout) in gastric cancer cells.
- In vivo xenograft models to evaluate peritoneal metastasis.
- Analysis of NADPH levels, reactive oxygen species (ROS), and protein ubiquitination/phosphorylation (NADK1).
Main Results
- GPER1 promotes gastric cancer peritoneal metastasis by inhibiting anoikis.
- GPER1 activation influences NADPH levels and ROS generation.
- GPER1 regulates nicotinamide adenine dinucleotide kinase 1 (NADK1) stability and activity through ubiquitination and phosphorylation.
- Inhibition of NADK1 disrupts redox homeostasis, increases ROS, induces anoikis, and reduces metastasis.
Conclusions
- GPER1 is a critical mediator of gastric cancer peritoneal metastasis.
- The GPER1-NADK1 axis plays a significant role in regulating cancer cell survival and metastasis.
- Targeting GPER1-mediated NADK1 activity presents a potential therapeutic strategy for gastric cancer peritoneal metastasis.
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