The SDC1-ENO1 Axis in Cancer-Associated Fibroblasts Generates a Lactate-Rich Microenvironment that Drives Tumor Radioresistance - PubMed
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- #lactate microenvironment
- #tumor radioresistance
- #SDC1-ENO1 axis
- SDC1 is identified as a key mediator of cancer-associated fibroblast (CAF)-induced radioresistance in triple-negative breast cancer (TNBC).
- SDC1 binds to the TIM barrel domain of ENO1, preventing its degradation by FBXW7, which drives aerobic glycolysis and lactate accumulation.
- The lactate-rich microenvironment promotes tumor stemness and impairs the cytotoxic functions of NK cells and CD8+ T cells.
- Pharmacologic inhibition of ENO1 or lactate export can restore radiosensitivity in tumors.
- Targeting SDC1+ CAFs with indatuximab ravtansine (BT062) synergizes with radiotherapy, reducing tumor burden and remodeling the immune microenvironment.