Blocking CEMIP2-Mediated Low-Molecular-Weight Hyaluronic Acid -TGFβ Signaling Inhibits Chemotherapy-Associated Lymphatic Metastasis in Gastric Cancer - PubMed
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- #CEMIP2 Signaling
- #Gastric Cancer
- #Chemotherapy-Associated Metastasis
- Chemotherapy-associated lymphatic metastasis is a major cause of treatment failure in gastric cancer, particularly during neoadjuvant chemotherapy.
- Hyaluronidase-driven degradation of hyaluronic acid (HA) is a key mechanism, with cell migration inducing hyaluronidase 2 (CEMIP2) being highly expressed and degrading HA into low molecular weight HA (LMWHA).
- CEMIP2-generated LMWHA activates CD44-ATF3 signaling, which transcriptionally upregulates TGFβ receptor TGFBR1, driving lymphatic metastasis.
- CEMIP2 is naturally highly expressed in gastric epithelium, making it a potential therapeutic target.
- Bioengineered iRGD-conjugated exosome mimics (EMs) were developed for targeted delivery of CEMIP2 siRNA, effectively suppressing chemotherapy-associated lymphatic metastasis in vivo.
- Targeting CEMIP2-mediated LMWHA-TGFβ signaling can inhibit chemotherapy-associated lymphatic metastasis, positioning CEMIP2 as a therapeutic target for gastric cancer.