ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2023; 14(17):3295-3308. doi:10.7150/jca.84652 This issue Cite
Research Paper
Ablation of the GDP-fucose transporter suppresses lung cancer cell proliferation and migration by reducing expression of PD-L1
1. Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
2. Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, 116001, China.
3. Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.
4. College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, China.
* Yingshu Zhang, Nianzhu Zhang and Wanli Song contributed equally to this work.
Abstract
Fucosylation, an important post-translational modification, is closely related to the development of tumors. In the microenvironment of lung cancer, expression of PD-L1 and fucosylation is abnormally upregulated. However, the correlation between PD-L1 expression and its fucosylation in lung adenocarcinoma (LUAD) remains unclear. The GDP-fucose transporter (GFT) is a key molecule in cellular fucosylation. To explore the correlation between fucosylation and PD-L1 expression, we knocked out the GFT-encoding gene SLC35C1 in mouse Lewis lung adenocarcinoma cells and in human H1299 lung adenocarcinoma cells. Loss of SLC35C1 impaired the phosphorylation of EGFR and its downstream target ERK. Moreover, loss of SLC35C1 up-regulated the expression of β-TrCP, a PD-L1 E3 ligase, thereby promoting the ubiquitination of PD-L1 and its subsequent degradation. The down-regulated expression of PD-L1 leads to a decline in lung cancer cell proliferation and migration. These results suggest that fucosylation partially influences LUAD tumorigenesis by regulating PD-L1 expression.
Keywords: Fucosylation, GDP-fucose transporter, Lung adenocarcinoma, PD-L1 ubiquitination, EGFR
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