This review discusses the role of E-cadherin and N-cadherin in epithelial-to-mesenchymal transition (EMT) in cancer, highlighting their signaling pathways, therapeutic implications, and challenges. EMT is crucial in tumorigenesis, enhancing metastasis, chemoresistance, and tumor stemness. The hallmark of EMT is the upregulation of N-cadherin and downregulation of E-cadherin, regulated by complex signaling pathways and transcription factors. E-cadherin is a potent tumor suppressor, while N-cadherin is associated with more aggressive cancers. The "cadherin switch" during EMT is linked to enhanced migratory and invasive traits. E-cadherin and N-cadherin have distinct roles in signaling pathways, with E-cadherin suppressing Wnt/β-catenin and RTK/P13K pathways, while N-cadherin activates MAPK/ERK and PI3K pathways. EMT is regulated by various transcription factors, including SNAIL, TWIST, and ZEB, and is influenced by signaling pathways such as TGF-β, MAPK, JAK/STAT, Hedgehog, and Wnt. Therapeutic strategies targeting EMT include shRNA, miRNA, small molecules, monoclonal antibodies, and natural compounds like curcumin, which can inhibit EMT and promote tumor suppression. Challenges in translating EMT research into clinical applications remain, emphasizing the need for further investigation into the molecular mechanisms and potential therapeutic interventions.This review discusses the role of E-cadherin and N-cadherin in epithelial-to-mesenchymal transition (EMT) in cancer, highlighting their signaling pathways, therapeutic implications, and challenges. EMT is crucial in tumorigenesis, enhancing metastasis, chemoresistance, and tumor stemness. The hallmark of EMT is the upregulation of N-cadherin and downregulation of E-cadherin, regulated by complex signaling pathways and transcription factors. E-cadherin is a potent tumor suppressor, while N-cadherin is associated with more aggressive cancers. The "cadherin switch" during EMT is linked to enhanced migratory and invasive traits. E-cadherin and N-cadherin have distinct roles in signaling pathways, with E-cadherin suppressing Wnt/β-catenin and RTK/P13K pathways, while N-cadherin activates MAPK/ERK and PI3K pathways. EMT is regulated by various transcription factors, including SNAIL, TWIST, and ZEB, and is influenced by signaling pathways such as TGF-β, MAPK, JAK/STAT, Hedgehog, and Wnt. Therapeutic strategies targeting EMT include shRNA, miRNA, small molecules, monoclonal antibodies, and natural compounds like curcumin, which can inhibit EMT and promote tumor suppression. Challenges in translating EMT research into clinical applications remain, emphasizing the need for further investigation into the molecular mechanisms and potential therapeutic interventions.