Abstract 1874: Glycoproteome and surfaceome mapping of epithelial-to-mesenchymal transition reveals key ion channel regulation and novel biomarkers in cancer metastasis

Abstract The epithelial-to-mesenchymal transition (EMT) is a crucial process driving cancer metastasis. In this transition, cell morphologies and properties are dramatically changed, but the underlying molecular mechanisms remain to be explored. In this work, we performed a comprehensive analysis of the proteome, the glycoproteome, and the surfaceome during the EMT process induced in A549 lung carcinoma cells using mass spectrometry-based proteomics. We identified five distinct EMT states characterized by alterations in protein expression and N-glycosylation patterns. We characterized 8,891 proteins, including 1,366 N-glycoproteins and 635 surface glycoproteins, and further bioinformatic analyses provide valuable insights into the mechanisms of EMT. Notably, we observed significant regulation of sodium, chloride, and calcium ion channels during EMT, underscoring their importance in cancer metastasis. Surface glycoproteins such as MET and SLC2A1 emerged as potential biomarkers for partial EMT, paving the way for advancements in early cancer diagnosis and targeted therapies. Furthermore, our findings reveal that EMT-associated N-glycosylation occurs in specific protein domains and aggregation-prone regions (APRs), affecting protein stability and trafficking. This work advances our understanding of the molecular mechanisms of EMT and underscores the therapeutic potential of targeting glycoproteins and ion channels in metastatic cancer. Citation Format: Xing Xu, Kejun Yin, Ronghu Wu. Glycoproteome and surfaceome mapping of epithelial-to-mesenchymal transition reveals key ion channel regulation and novel biomarkers in cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1874.