GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway
Autophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mecha...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.656608/full |
| _version_ | 1818918632954003456 |
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| author | Chunsen Li Zhenzhen Li Lingxie Song Lingxie Song Lian Meng Guixuan Xu Haijun Zhang Jianming Hu Feng Li Feng Li Chunxia Liu Chunxia Liu |
| author_facet | Chunsen Li Zhenzhen Li Lingxie Song Lingxie Song Lian Meng Guixuan Xu Haijun Zhang Jianming Hu Feng Li Feng Li Chunxia Liu Chunxia Liu |
| author_sort | Chunsen Li |
| collection | DOAJ |
| description | Autophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mechanisms of autophagy and apoptosis are unclear. In our study, we found that the RMS tissues had high Rac1, Cdc42, mTOR, and Bcl-2 expression levels and low Beclin1, LC3, and Bax expression levels compared with the normal striated muscle tissues (P < 0.05). In addition, multivariate analysis has proven that Rac1 is an independent prognostic factor (P < 0.05), and the high expression level of the Beclin1 protein was closely associated with the tumor diameter of the RMS patients (P = 0.044), whereas the high expression level of the LC3 protein was associated with the clinical stage of the RMS patients (P = 0.027). Furthermore, GEFT overexpression could inhibit autophagy and apoptosis in RMS. A Rac1/Cdc42 inhibitor was added, and the inhibition of autophagy and apoptosis decreased. Rac1 and Cdc42 could regulate mTOR to inhibit autophagy and apoptosis in RMS. Overall, these studies demonstrated that the GEFT–Rac1/Cdc42–mTOR pathway can inhibit autophagy and apoptosis in RMS and provide evidence for innovative treatments. |
| first_indexed | 2024-12-20T00:53:03Z |
| format | Article |
| id | doaj.art-12eba07b59c34451913e98b2dad551b6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T00:53:03Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-12eba07b59c34451913e98b2dad551b62022-12-21T19:59:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.656608656608GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling PathwayChunsen Li0Zhenzhen Li1Lingxie Song2Lingxie Song3Lian Meng4Guixuan Xu5Haijun Zhang6Jianming Hu7Feng Li8Feng Li9Chunxia Liu10Chunxia Liu11Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaAutophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mechanisms of autophagy and apoptosis are unclear. In our study, we found that the RMS tissues had high Rac1, Cdc42, mTOR, and Bcl-2 expression levels and low Beclin1, LC3, and Bax expression levels compared with the normal striated muscle tissues (P < 0.05). In addition, multivariate analysis has proven that Rac1 is an independent prognostic factor (P < 0.05), and the high expression level of the Beclin1 protein was closely associated with the tumor diameter of the RMS patients (P = 0.044), whereas the high expression level of the LC3 protein was associated with the clinical stage of the RMS patients (P = 0.027). Furthermore, GEFT overexpression could inhibit autophagy and apoptosis in RMS. A Rac1/Cdc42 inhibitor was added, and the inhibition of autophagy and apoptosis decreased. Rac1 and Cdc42 could regulate mTOR to inhibit autophagy and apoptosis in RMS. Overall, these studies demonstrated that the GEFT–Rac1/Cdc42–mTOR pathway can inhibit autophagy and apoptosis in RMS and provide evidence for innovative treatments.https://www.frontiersin.org/articles/10.3389/fonc.2021.656608/fullautophagyapoptosisRac1Cdc42mTOR |
| spellingShingle | Chunsen Li Zhenzhen Li Lingxie Song Lingxie Song Lian Meng Guixuan Xu Haijun Zhang Jianming Hu Feng Li Feng Li Chunxia Liu Chunxia Liu GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway Frontiers in Oncology autophagy apoptosis Rac1 Cdc42 mTOR |
| title | GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway |
| title_full | GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway |
| title_fullStr | GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway |
| title_full_unstemmed | GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway |
| title_short | GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway |
| title_sort | geft inhibits autophagy and apoptosis in rhabdomyosarcoma via activation of the rac1 cdc42 mtor signaling pathway |
| topic | autophagy apoptosis Rac1 Cdc42 mTOR |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.656608/full |
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