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FOXA2 loss in TGF-β1-induced EMT suppresses bisecting-GlcNAc N-glycan synthesis in lung adenocarcinoma
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  • Wei Ge,
  • Shengye Wen,
  • Xiaoli Zhou,
  • Yan Chen,
  • Daxiong Zeng,
  • Junhong Jiang,
  • Shuang Yang
Wei Ge
The Fourth Affiliated Hospital of Soochow University
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Shengye Wen
Soochow University
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Xiaoli Zhou
The Fourth Affiliated Hospital of Soochow University
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Yan Chen
Soochow University
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Daxiong Zeng
The Fourth Affiliated Hospital of Soochow University
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Junhong Jiang
The Fourth Affiliated Hospital of Soochow University
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Shuang Yang
Soochow University

Corresponding Author:[email protected]

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Abstract

Glycosylation, a significant form of post-translational modification (PTM) in organisms, is aberrantly expressed in cancer due to altered glycosyltransferase activity. Studies have shown specific changes in glycan structures associated with epithelial-mesenchymal transition (EMT) of cancer cells. This study analyzed glycans in bronchoalveolar lavage fluid (BALF) from lung adenocarcinoma (LUAD) patients and found a significant reduction in glycans containing the bisecting-GlcNAc structure. Further investigation revealed that reduced expression of β-1,4-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase (MGAT3) downregulates epithelial markers, promoting EMT. Additionally, we observed a notable downregulation of both mRNA and protein expression of Forkhead box protein A2 (FOXA2) in early-stage LUAD, with FOXA2 loss emerging as an adverse prognostic indicator. Cellular models demonstrated that FOXA2 deficiency decreased MGAT3 expression during TGF-β1-driven EMT, leading to reduced levels of bisecting-GlcNAc N-glycans in LUAD cells. Our findings unveil a novel mechanism underlying the downregulation of MGAT3 and bisecting GlcNAc N-glycan expression during EMT, a process crucial for tumor metastasis.
Submitted to PROTEOMICS
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05 Jul 2024Reviewer(s) Assigned
06 Aug 2024Review(s) Completed, Editorial Evaluation Pending
15 Aug 2024Editorial Decision: Revise Minor