Advances in molecular mechanism of gastric cancer peritoneal metastasis

Table 3 Summary of key molecules and signaling pathways driving epithelial-mesenchymal transition and extracellular matrix remodeling in gastric cancer peritoneal metastasis

Category	Key molecule/pathway	Mechanism of action	Functional	Clinical potential
EMT drivers	CST1	Stabilizes GPX4 to inhibit ferroptosis; upregulates N-cadherin/Snail, downregulates E-cadherin	Synergistically drives EMT and tumor invasion	Prognostic biomarker and combination targeting strategy
	BGN/FAP/STAT3 loop	BGN binds TLR2/4 on mesothelial cells → NF-κB activation → mesothelial-to-CAF transition; CAFs secrete FAP → forms positive feedback loop	Continuous EMT activation	Prediction of biomarkers and therapeutic targets
	APOC2/CD36	Activates PI3K/AKT/mTOR pathway via CD36 receptor	Upregulates mesenchymal markers and MMPs	Therapeutic target
	CD44/STAT3	Signaling integration platform cooperating with STAT3	Initiates EMT transcriptional reprogramming	Therapeutic target
ECM remodeling	MMPs	Degrade ECM barrier and release matrix-bound growth factors	Promote invasion and metastasis	Prognostic biomarkers
	LOX	Catalyzes collagen crosslinking → increased matrix stiffness; remote pre-conditioning of metastatic niche	Promotes invasion, EMT, and immunosuppression	Prognostic biomarker and therapeutic target
EMT-ECM crosstalk	FERMT2/SOX2/FN1	Stabilizes SOX2 → activates FN1 transcription → guides fibronectin matrix remodeling	Promotes tumor cells survival, invasion, and metastasis	Therapeutic target
	GRP94/YAP/TEAD1	Upregulates IL6 expression → activates YAP/TEAD1 pathway	Anoikis resistance; promotes migration and invasion	Therapeutic target
	CTSL, macrophage-derived	Degrades ECM components; promotes M2 macrophage polarization	Promotes EMT and invasion	Dual-effect target
	Exosomal miR-106a	Delivered to mesothelial cells → activates TGF-β signaling → induces MMT	Disrupts peritoneal integrity; establishes pre-metastatic niche	Diagnostic/prognostic biomarker and therapeutic target

This table catalogs the major molecular regulators of epithelial-mesenchymal transition and extracellular matrix remodeling in gastric cancer peritoneal metastasis. It summarizes their mechanisms of action, functional consequences, and translational potential. EMT: Epithelial-mesenchymal transition; CST1: Cystatin SN; GPX4: Glutathione peroxidase 4; BGN: Biglycan; FAP: Fibronectin attachment protein; STAT3: Signal transducer and activator of transcription 3; TLR2/4: Toll-like receptor 2/4; NF-κB: Nuclear factor-kappa B; CAF: Cancer-associated fibroblast; APOC2: Apolipoprotein C2; PI3K: Phosphatidylinositide 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; MMPs: Matrix metalloproteinases; ECM: Extracellular matrix; LOX: Lysyl oxidase; FERMT2: Fermitin family homolog-2; SOX2: SRY box 2; FN1: Fibronectin 1; GRP94: Glucose-regulated protein 94; TEAD1: TEA domain transcription factor 1; CTSL: Cathepsin L; TGF: Transforming growth factor; MMT: Mesothelial-mesenchymal transition.