Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2
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...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/22/5688 |
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| author | Fuyang Cao Desong Yang Feiyu Tang Can Lu Xiang He Songming Chen Zhanghuan Yang Siyuan Gong Lunquan Sun Atsushi Enomoto Masahide Takahashi Liang Weng |
| author_facet | Fuyang Cao Desong Yang Feiyu Tang Can Lu Xiang He Songming Chen Zhanghuan Yang Siyuan Gong Lunquan Sun Atsushi Enomoto Masahide Takahashi Liang Weng |
| author_sort | Fuyang Cao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T18:25:36Z |
| format | Article |
| id | doaj.art-a6a4bf7965db40418bfda8eeb38c4ebc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T18:25:36Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a6a4bf7965db40418bfda8eeb38c4ebc2023-11-24T07:55:08ZengMDPI AGCancers2072-66942022-11-011422568810.3390/cancers14225688Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2Fuyang Cao0Desong Yang1Feiyu Tang2Can Lu3Xiang He4Songming Chen5Zhanghuan Yang6Siyuan Gong7Lunquan Sun8Atsushi Enomoto9Masahide Takahashi10Liang Weng11Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaHunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanInternational Center for Cell and Gene Therapy, Fujita Health University, Toyoake 470-1192, JapanDepartment of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, ChinaGirdin, 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.https://www.mdpi.com/2072-6694/14/22/5688GirdinPKM2tumorigenesischemoresistanceLUAD |
| spellingShingle | Fuyang Cao Desong Yang Feiyu Tang Can Lu Xiang He Songming Chen Zhanghuan Yang Siyuan Gong Lunquan Sun Atsushi Enomoto Masahide Takahashi Liang Weng Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2 Cancers Girdin PKM2 tumorigenesis chemoresistance LUAD |
| title | Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2 |
| title_full | Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2 |
| title_fullStr | Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2 |
| title_full_unstemmed | Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2 |
| title_short | Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2 |
| title_sort | girdin promotes tumorigenesis and chemoresistance in lung adenocarcinoma by interacting with pkm2 |
| topic | Girdin PKM2 tumorigenesis chemoresistance LUAD |
| url | https://www.mdpi.com/2072-6694/14/22/5688 |
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