Glucose metabolism sustains aberrant STAT3 signaling in colorectal cancer through glycosylated local signaling factors - PubMed
4 hours ago
- #colorectal cancer
- #STAT3 signaling
- #glucose metabolism
- The JAK-STAT3 signaling pathway is crucial for colorectal cancer (CRC) progression.
- STAT3 is typically activated transiently by cytokines like IL-6 but remains persistently active in CRC, promoting tumor growth.
- Glucose and its metabolite GlcNAc are essential for maintaining STAT3 activation independently of cytokines.
- Glucose-dependent glycosylation of proteins enables paracrine STAT3 activation in neighboring cells.
- Proteomic analysis suggests multiple glycosylated proteins collectively activate STAT3, with no single protein being sufficient.
- Inhibition of glycolysis reduces STAT3 activation in CRC tumors in mouse models.
- Genetic deletion of STAT3 significantly decreases tumor growth, indicating its critical role.
- The findings reveal a metabolic vulnerability in CRC, suggesting glycolysis as a therapeutic target.