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Background <p>Cadherin family genes (<i>CDH1</i>, <i>CDH2</i>, and <i>CDH3</i>) regulate cell–cell adhesion and epithelial integrity and have emerging roles in tumorigenesis. However, their molecular and functional relevance in Head and Neck Squamous Cell Carcinoma (HNSC) remains incompletely defined.</p> Methods <p>Cadherin expression was evaluated in HNSC and normal oral epithelial cell lines using RT-qPCR. Multi-omics analyses of transcriptomic, methylation, mutation, and copy number variation (CNV) data were performed using TCGA datasets through GSCA, OncoDB, cBioPortal, and UALCAN. Prognostic significance was assessed using Kaplan–Meier and meta-analysis approaches. miRNA–mRNA interactions were predicted using miRNet and validated experimentally. Immune associations, drug sensitivity, and protein–protein interactions were explored using TISIDB, GSCA, STRING, and DAVID. Functional effects of <i>CDH1</i> and <i>CDH2</i> were evaluated by siRNA knockdown in FaDu and SCC9 cells, followed by proliferation, colony formation, wound healing, and xenograft assays.</p> Results <p><i>CDH1</i>, <i>CDH2</i>, and <i>CDH3</i> were significantly upregulated in HNSC cell lines and TCGA tumor samples, with <i>CDH3</i> showing the highest diagnostic accuracy (AUC = 0.90). Hypomethylation and CNV amplification contributed to cadherin dysregulation, particularly for <i>CDH2</i> and <i>CDH3</i>. Elevated cadherin expression correlated with poor overall survival. miR-200a-3p and miR-200c-3p were identified as shared regulators. Cadherin expression also showed associations with immune modulators and drug response. Functionally, <i>CDH1</i> and <i>CDH2</i> knockdown suppressed proliferation, migration, and tumor growth.</p> Conclusion <p>Cadherin genes, particularly <i>CDH3</i>, show diagnostic and prognostic relevance in HNSC, while <i>CDH1</i> and <i>CDH2</i> contribute to tumor cell growth and migration. Further studies are required to determine their therapeutic potential.</p>

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Cadherin-mediated cell adhesion networks drive tumor growth and therapeutic responses in head and neck cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Mostafa A. Abdel-Maksoud,
  • Abdulaziz Alamri,
  • Aljawharah Fahad,
  • Salman Alrokayan,
  • Mohammed Aufy,
  • Bushra Hafeez Kiani,
  • Hanyong Zhang,
  • Muhammad Mazhar Ayaz,
  • Yasir Hameed,
  • Saeedah Almutairi

摘要

Background

Cadherin family genes (CDH1, CDH2, and CDH3) regulate cell–cell adhesion and epithelial integrity and have emerging roles in tumorigenesis. However, their molecular and functional relevance in Head and Neck Squamous Cell Carcinoma (HNSC) remains incompletely defined.

Methods

Cadherin expression was evaluated in HNSC and normal oral epithelial cell lines using RT-qPCR. Multi-omics analyses of transcriptomic, methylation, mutation, and copy number variation (CNV) data were performed using TCGA datasets through GSCA, OncoDB, cBioPortal, and UALCAN. Prognostic significance was assessed using Kaplan–Meier and meta-analysis approaches. miRNA–mRNA interactions were predicted using miRNet and validated experimentally. Immune associations, drug sensitivity, and protein–protein interactions were explored using TISIDB, GSCA, STRING, and DAVID. Functional effects of CDH1 and CDH2 were evaluated by siRNA knockdown in FaDu and SCC9 cells, followed by proliferation, colony formation, wound healing, and xenograft assays.

Results

CDH1, CDH2, and CDH3 were significantly upregulated in HNSC cell lines and TCGA tumor samples, with CDH3 showing the highest diagnostic accuracy (AUC = 0.90). Hypomethylation and CNV amplification contributed to cadherin dysregulation, particularly for CDH2 and CDH3. Elevated cadherin expression correlated with poor overall survival. miR-200a-3p and miR-200c-3p were identified as shared regulators. Cadherin expression also showed associations with immune modulators and drug response. Functionally, CDH1 and CDH2 knockdown suppressed proliferation, migration, and tumor growth.

Conclusion

Cadherin genes, particularly CDH3, show diagnostic and prognostic relevance in HNSC, while CDH1 and CDH2 contribute to tumor cell growth and migration. Further studies are required to determine their therapeutic potential.