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

  • Pathol Res Pract. 2025 Aug:272:156042. doi: 10.1016/j.prp.2025.156042.
Lin Xiao  1 ,  Bingbing Yang  2 ,  Yijuan Zhou  2 ,  Jiarui Zhang  2 ,  Xiaoyan Zhang  2 ,  Wanjing Yang  2 ,  Minjing Sun  1 ,  Mengmeng Li  1 ,  Xueyan Zhao  3 ,  Fang Tian  4
Affiliations
  • 1. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China.
  • 2. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
  • 3. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: [email protected].
  • 4. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China; Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: [email protected].
PMID: 40460640 DOI: 10.1016/j.prp.2025.156042
Abstract

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.

Keywords
2; 5-DiMethyl Celecoxib; Cadherin-11; Celecoxib; Esophageal squamous cell carcinoma.
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