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Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2.

Authors :
Cao, Fuyang
Yang, Desong
Tang, Feiyu
Lu, Can
He, Xiang
Chen, Songming
Yang, Zhanghuan
Gong, Siyuan
Sun, Lunquan
Enomoto, Atsushi
Takahashi, Masahide
Weng, Liang
Source :
Cancers. Nov2022, Vol. 14 Issue 22, p5688. 16p.
Publication Year :
2022

Abstract

Simple Summary: Aerobic glycolysis is a key driving force of tumorigenesis and chemoresistance. Girdin plays a vital role in cancer cells; however, the role of Girdin in aerobic glycolysis is still unclear. In this study, we first found that knockout of Girdin markedly inhibited lung adenocarcinoma (LUAD) progression in an autochthonous LUAD mouse model. In addition, we found that Girdin interacted with pyruvate kinase M2 (PKM2) and impaired PKM2 activity, which promoted the Warburg effect and chemoresistance. Our results suggest that Girdin is a potential therapeutic target to overcome the resistance of LUAD cells to chemotherapeutic agents. Girdin, an Akt substrate, has been reported to promote tumorigenesis in various tumors. However, the role of Girdin in a spontaneous tumor model has not yet been explored. Here, we studied the role of Girdin in lung adenocarcinoma (LUAD) using the autochthonous mouse model and found that Girdin led to LUAD progression and chemoresistance by enhancing the Warburg effect. Mechanistically, Girdin interacted with pyruvate kinase M2 (PKM2), which played a vital role in aerobic glycolysis. Furthermore, Girdin impaired Platelet Derived Growth Factor Receptor Beta (PDGFRβ) degradation, which in turn, promoted PKM2 tyrosine residue 105 (Y105) phosphorylation and inhibited PKM2 activity, subsequently promoting aerobic glycolysis in cancer cells. Taken together, our study demonstrates that Girdin is a crucial regulator of tumor growth and may be a potential therapeutic target for overcoming the resistance of LUAD cells to chemotherapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726694
Volume :
14
Issue :
22
Database :
Academic Search Index
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
160434722
Full Text :
https://doi.org/10.3390/cancers14225688