Detachment-Induced FAK-STAT3-NNMT Inhibits CTCs Anoikis to Promote Breast Cancer Metastasis by Enhancing Fatty Acid Oxidation - PubMed
7 hours ago
- #CTCs
- #Metastasis
- #Breast Cancer
- Breast cancer metastasis is a major cause of breast cancer-related deaths.
- Anoikis resistance is crucial for circulating tumor cells (CTCs) survival and metastasis.
- Nicotinamide N-methyltransferase (NNMT) is upregulated in CTCs from breast cancer patients and mouse models.
- NNMT is induced by the FAK-STAT3 axis in detached breast cancer cells, promoting anoikis resistance through fatty acid oxidation (FAO) activation.
- NNMT enhances FAO by suppressing PP2A methylation, increasing CPT1A and CD36 expression.
- NNMT-induced FAO helps clear reactive oxygen species (ROS) by maintaining NADP+/NADPH balance.
- Targeting NNMT or FAO reduces lung metastases in vivo, suggesting potential therapeutic strategies.
- The study highlights NNMT as a potential therapeutic target for metastatic breast cancer.