High expression of SLC2A1 inhibits ferroptosis and promotes proliferation and invasion of lung adenocarcinoma cells.
10.12122/j.issn.1673-4254.2024.12.17
- Author:
Hong KUANG
1
;
Wenhan CAI
1
;
Yiming LIU
1
;
Jiaxin WEN
1
;
Shuo TIAN
1
;
Zhiqiang XUE
1
Author Information
1. Department of Thoracic Surgery, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
- Publication Type:Journal Article
- Keywords:
autophagy;
ferroptosis;
glucose transporter 1;
lung adenocarcinoma
- MeSH:
Humans;
Ferroptosis/genetics*;
Cell Proliferation;
Adenocarcinoma of Lung/genetics*;
Lung Neoplasms/genetics*;
Cell Line, Tumor;
Cell Movement;
Glucose Transporter Type 1/genetics*;
Prognosis;
Autophagy;
Neoplasm Invasiveness;
Female;
Male
- From:
Journal of Southern Medical University
2024;44(12):2404-2411
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To examine how the glucose transporter SLC2A1 influences the proliferation and migration of lung adenocarcinoma (LUAD) and explore the underlying molecular mechanisms.
METHODS:We examined the differential expression of SLC2A1 between normal and LUAD tissues in the TCGA database and its prognostic implications. Immunohistochemistry was used to detect SLC2A1 protein levels in clinical samples of LUAD and adjacent tissues, and the association of SLC2A1 expression levels with clinicopathological features of the patients was analyzed. In PC9 cells with stable SLC2A1 overexpression or knockdown, the effects of SLC2A1 expression level on cell proliferation and migration were assessed using CCK-8 and Transwell assays, and the changes in expressions of ferroptosis- and autophagy-related proteins were measured; the occurrence of ferroptosis was confirmed using ROS and Fe2+ fluorescence staining.
RESULTS:SLC2A1 expression was significantly higher in LUAD tumor tissues than in normal lung tissues (P<0.05) and was associated with worse pathological parameters and prognosis of the patients (P<0.05). In PC9 cells, SLC2A1 overexpression significantly promoted cell proliferation, invasion and migration, and SLC2A1 knockdown significanty increased cell death and inhibited cell invasion and proliferation. SLC2A1 knockdown caused obvious activation of cell ferroptosis, reduced GPX4 and xCT expressions, and increased intracellular levels of ROS and Fe2+. SLC2A1 knockdown also resulted in increased cell autophagy shown by increased LC3B expression, which could be reversed by treatement with 3-MA.
CONCLUSIONS:High SLC2A1 expression is correlated with poor prognosis of patients with LUAD, and inhibiting SLC2A1 can induce ferroptosis and autophagy of LUAD cells, suggesting the potential of SLC2A1 as a target for LUAD diagnosis and treatment.
