Targeting CDH11 with celecoxib and derivatives to suppress esophageal squamous cell carcinoma proliferation and invasion.

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with limited therapeutic options. Cadherin-11 (CDH11) has been implicated in tumor progression, but its role in ESCC remains unclear.

METHODS

CDH11 expression was analyzed in ESCC tissues and cell lines. Functional assays (proliferation, migration, invasion) and xenograft models were employed to assess CDH11's role. Celecoxib and its derivative 2,5-dimethyl celecoxib (DMC) were evaluated as CDH11-targeted inhibitors.

RESULTS

CDH11 was overexpressed in ESCC tissues and correlated with lymph node metastasis and poor prognosis. Knockdown of CDH11 suppressed ESCC proliferation and invasion (P < 0.05), while overexpression exacerbated these phenotypes. Celecoxib and DMC directly bound CDH11 and inhibited ESCC growth in vitro and in vivo (IC50: 21.61-43.34 μM). Mechanistically, CDH11 knockdown attenuated JAK-STAT3 and AKT signaling.

CONCLUSION

CDH11 is a novel therapeutic target in ESCC, and its inhibition by celecoxib/DMC offers a promising strategy for ESCC treatment.