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

Fuyang Cao; Desong Yang; Feiyu Tang; Can Lu; Xiang He; Songming Chen; Zhanghuan Yang; Siyuan Gong; Lunquan Sun; Atsushi Enomoto; Masahide Takahashi; Liang Weng

doi:10.3390/cancers14225688

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

Fuyang Cao, Desong Yang, Feiyu Tang, Can Lu, Xiang He, Songming Chen, Zhanghuan Yang, Siyuan Gong, Lunquan Sun, Atsushi Enomoto, Masahide Takahashi, Liang Weng

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Abstract

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.

Original language	English
Article number	5688
Journal	Cancers
Volume	14
Issue number	22
DOIs	https://doi.org/10.3390/cancers14225688
Publication status	Published - 11-2022

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers14225688

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title = "Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2",

abstract = "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.",

keywords = "Girdin, LUAD, PKM2, chemoresistance, tumorigenesis",

author = "Fuyang Cao and Desong Yang and Feiyu Tang and Can Lu and Xiang He and Songming Chen and Zhanghuan Yang and Siyuan Gong and Lunquan Sun and Atsushi Enomoto and Masahide Takahashi and Liang Weng",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

doi = "10.3390/cancers14225688",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

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TY - JOUR

T1 - Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2

AU - Cao, Fuyang

AU - Yang, Desong

AU - Tang, Feiyu

AU - Lu, Can

AU - He, Xiang

AU - Chen, Songming

AU - Yang, Zhanghuan

AU - Gong, Siyuan

AU - Sun, Lunquan

AU - Enomoto, Atsushi

AU - Takahashi, Masahide

AU - Weng, Liang

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

KW - Girdin

KW - LUAD

KW - PKM2

KW - chemoresistance

KW - tumorigenesis

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U2 - 10.3390/cancers14225688

DO - 10.3390/cancers14225688

M3 - Article

AN - SCOPUS:85142486255

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 22

M1 - 5688

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

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