loading page

FOXA2 loss in TGF-β1-induced EMT suppresses bisecting-GlcNAc N-glycan synthesis in lung adenocarcinoma
  • +4
  • Wei Ge,
  • Shengye Wen,
  • Xiaoli Zhou,
  • Yan Chen,
  • Daxiong Zeng,
  • Junhong Jiang,
  • Shuang Yang
Wei Ge
The Fourth Affiliated Hospital of Soochow University
Author Profile
Shengye Wen
Soochow University
Author Profile
Xiaoli Zhou
The Fourth Affiliated Hospital of Soochow University
Author Profile
Yan Chen
Soochow University
Author Profile
Daxiong Zeng
The Fourth Affiliated Hospital of Soochow University
Author Profile
Junhong Jiang
The Fourth Affiliated Hospital of Soochow University
Author Profile
Shuang Yang
Soochow University

Corresponding Author:yangs2020@suda.edu.cn

Author Profile

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
Assigned to Editor
Reviewer(s) Assigned
Submission Checks Completed
05 Jul 2024Reviewer(s) Assigned
06 Aug 2024Review(s) Completed, Editorial Evaluation Pending
15 Aug 2024Editorial Decision: Revise Minor