ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment - PubMed
5 hours ago
- #asparagine metabolism
- #colorectal cancer
- #ETV4
- ETV4 is identified as a key factor in colorectal cancer (CRC) progression, integrating oncogenic signaling, metabolism, and stromal remodeling.
- HGF/MET signaling induces ETV4 via an ERK1/2-p65 pathway, which in turn activates MET and asparagine synthetase (ASNS), creating a positive feedback loop.
- Tumor-derived asparagine (Asn) promotes inflammatory cancer-associated fibroblast (iCAF) activation in hepatic stellate cells (HSCs) and primary CAFs, enhancing HGF secretion.
- Disruption of the HGF/MET → ETV4 → MET/ASNS → asparagine → iCAFs circuit attenuates CRC growth and metastasis in models.
- Combined inhibition of HGF/MET signaling and Asn metabolism shows greater antitumor activity than monotherapy, suggesting a therapeutic strategy for advanced CRC.