D-mannose suppresses the angiogenesis and progression of colorectal cancer

• D-mannose suppresses colorectal cancer angiogenesis and tumor growth by promoting lysosomal degradation of VEGFR2. • Mechanistically, D-mannose inactivates GSK3β via Ser9 phosphorylation, leading to TFE3 nuclear translocation and enhanced lysosomal biogenesis. • D-mannose inhibits HUVEC proliferation, migration, and capillary formation in vitro, and oral administration reduces tumor angiogenesis in mice. • These findings propose D-mannose as a potential therapeutic agent for colorectal cancer by targeting VEGFR2 stability.