ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment

tumor cells. Genetic and pharmacologic disruption of this axis attenuates CRC growth and metastatic traits in vitro and in mouse models. Notably, combined inhibition of HGF/MET signaling and Asn metabolism produces greater antitumor activity than either monotherapy. Together, these data delineate an HGF/MET → ETV4 → MET/ASNS → asparagine → iCAFs and iCAF-like HSCs → HGF circuit that links signal amplification, metabolic reprogramming, and niche conditioning, and provide a rationale for therapeutic strategies co‑targeting HGF/MET and Asn pathways in advanced CRC.