B4GALNT1 promotes progression and metastasis in lung adenocarcinoma through JNK/c-Jun/Slug pathway

Tian Jiang; Hao Wu; Miao Lin; Jun Yin; Lijie Tan; Yuanyuan Ruan; Mingxiang Feng

doi:10.1093/carcin/bgaa141

B4GALNT1 promotes progression and metastasis in lung adenocarcinoma through JNK/c-Jun/Slug pathway

Carcinogenesis. 2021 Apr 30;42(4):621-630. doi: 10.1093/carcin/bgaa141.

Authors

Tian Jiang¹, Hao Wu^{2

3}, Miao Lin¹, Jun Yin¹, Lijie Tan¹, Yuanyuan Ruan², Mingxiang Feng¹

Affiliations

¹ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, China.
² Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ Department of Clinical Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

PMID: 33367717
DOI: 10.1093/carcin/bgaa141

Abstract

Lung adenocarcinoma (LUAD) is one of the most common types of cancer and has a low survival rate. β-1,4-N-Acetyl galactosaminyltransferase 1 (B4GALNT1), which is involved in the synthesis of complex gangliosides, is highly expressed in the progression of various cancers. This study aimed to elucidate the biological functions of B4GALNT1 in LUAD progression and metastasis. We observed that B4GALNT1 overexpression showed enhanced cell migration and invasion in vitro, and promoted tumor metastasis, with reduced survival in mice. Mechanistically, B4GALNT1 regulated metastatic potential of LUAD through activating the JNK/c-Jun/Slug pathway, and with the form of its enzymatic activity. Clinical samples confirmed that B4GALNT1 expression was upregulated in LUAD, and B4GALNT1 was correlated with c-Jun/Slug expression, lymph node involvement, advanced clinical stage, and reduced overall survival. Collectively, our results suggest that B4GALNT1 promotes progression and metastasis of LUAD through activating JNK/c-Jun/Slug signaling, and with the form of its enzymatic activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung / genetics*
Adenocarcinoma of Lung / pathology
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation / genetics
Disease Progression
Female
Gene Expression Regulation, Neoplastic / genetics
Heterografts
Humans
JNK Mitogen-Activated Protein Kinases / genetics*
MAP Kinase Kinase 4 / genetics*
Male
Mice
N-Acetylgalactosaminyltransferases / genetics*
Neoplasm Metastasis
Signal Transduction
Snail Family Transcription Factors / genetics*

Substances

SNAI1 protein, human
Snail Family Transcription Factors
N-Acetylgalactosaminyltransferases
B4galnt1 protein, human
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4