GLUT1 promotes cell proliferation via binds and stabilizes phosphorylated EGFR in lung adenocarcinoma

Zhiqing,Zhou1; Yu,Li1; Sijie,Chen1; Zhangrong,Xie1; Yuhui,Du1; Yue,Liu1; Yuxuan,Shi1; Xiangyi,Lin1; Xiaofei,Zeng1,2; Huijie,Zhao1,3; Guoan,Chen1,4

2024-06-03

10.1186/s12964-024-01678-8

Cell Communication and Signaling   影响因子和分区

1478-811X

1478-811X

Background While previous studies have primarily focused on Glucose transporter type 1 (GLUT1) related glucose metabolism signaling, we aim to discover if GLUT1 promotes tumor progression through a non-metabolic pathway.

Methods: The RNA-seq and microarray data were comprehensively analyzed to evaluate the significance of GLUT1 expression in lung adenocarcinoma (LUAD). The cell proliferation, colony formation, invasion, and migration were used to test GLUT1 ‘s oncogenic function. Co-immunoprecipitation and mass spectrum (MS) were used to uncover potential GLUT1 interacting proteins. RNA-seq, DIA-MS, western blot, and qRT-PCR to probe the change of gene and cell signaling pathways.

Results We found that GLUT1 is highly expressed in LUAD, and higher expression is related to poor patient survival. GLUT1 knockdown caused a decrease in cell proliferation, colony formation, migration, invasion, and induced apoptosis in LUAD cells. Mechanistically, GLUT1 directly interacted with phosphor-epidermal growth factor receptor (p-EGFR) and prevented EGFR protein degradation via ubiquitin-mediated proteolysis. The GLUT1 inhibitor WZB117 can increase the sensitivity of LUAD cells to EGFR-tyrosine kinase inhibitors (TKIs) Gefitinib.

Conclusions GLUT1 expression is higher in LUAD and plays an oncogenic role in lung cancer progression. Combining GLUT1 inhibitors and EGFR-TKIs could be a potential therapeutic option for LUAD treatment.

LUAD, GLUT1, EGFR, Gefitinib, WZB117

分子生物学

医学::基础医学（可授医学、理学学位）

SCI

英语

第一 ; 通讯

Shenzhen Municipal Science and Technology Innovation Commission Foundation ; the National Natural Science Foundation of China ; the Medical Science and Technology Research Fund project of Guangdong Province ; National Training Program of Undergraduate Innovation and Entrepreneurship

Springer Science and Business Media LLC

2-s2.0-85195013757

人工提交

在线出版

1.Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, China
2.National Key Laboratory for Tropical Crop Breeding, Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong 518120, China
3.Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
4.The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China

Zhiqing,Zhou,Yu,Li,Sijie,Chen,et al. GLUT1 promotes cell proliferation via binds and stabilizes phosphorylated EGFR in lung adenocarcinoma[J]. Cell Communication and Signaling,2024,22(1).

Zhiqing,Zhou.,Yu,Li.,Sijie,Chen.,Zhangrong,Xie.,Yuhui,Du.,...&Guoan,Chen.(2024).GLUT1 promotes cell proliferation via binds and stabilizes phosphorylated EGFR in lung adenocarcinoma.Cell Communication and Signaling,22(1).

Zhiqing,Zhou,et al."GLUT1 promotes cell proliferation via binds and stabilizes phosphorylated EGFR in lung adenocarcinoma".Cell Communication and Signaling 22.1(2024).