MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway

Abstract Epithelial‒mesenchymal transition (EMT) is a process in which polar epithelial cells transform into active mesenchymal cells and acquire invasion and migration capabilities (Cano CE, Motoo Y, Iovanna JL in Sci World J 10, 2010). EMT is involved in multiple physiological and pathological pro...

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Main Authors: Zigui Chen, Chao Liu, Wei Zheng, Zhilong Li, Yuanhui Tang, Jun Peng, Changfeng Miao, Dandan Zheng, Ying Xia
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87151-z
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author Zigui Chen
Chao Liu
Wei Zheng
Zhilong Li
Yuanhui Tang
Jun Peng
Changfeng Miao
Dandan Zheng
Ying Xia
author_facet Zigui Chen
Chao Liu
Wei Zheng
Zhilong Li
Yuanhui Tang
Jun Peng
Changfeng Miao
Dandan Zheng
Ying Xia
author_sort Zigui Chen
collection DOAJ
description Abstract Epithelial‒mesenchymal transition (EMT) is a process in which polar epithelial cells transform into active mesenchymal cells and acquire invasion and migration capabilities (Cano CE, Motoo Y, Iovanna JL in Sci World J 10, 2010). EMT is involved in multiple physiological and pathological processes in the human body. The occurrence of EMT involves many signal transduction pathways and complex molecular mechanisms related to calnexin, growth factors, transcription factors, and the microenvironment. EMT is closely related to the invasion and metastasis of tumour cells. The MYH9 gene is closely associated with tumour progression. However, the function and regulatory mechanism of MYH9 in tumour occurrence and development remain unclear. Herein, we revealed for the first time that the migration, invasion, and metastatic abilities of glioma cells decreased significantly after MYH9 expression was downregulated. Moreover, our results suggested that MYH9 regulated the epithelial‒mesenchymal transition (EMT) process in glioma cells via β-catenin. In this mechanism, MYH9 was shown to bind to β-catenin and to increase its protein level by recruiting the deubiquitinase USP2 to form a complex. This complex suppressed β-catenin protein degradation, ultimately enhancing EMT signal transduction. This MYH9/β-catenin/EMT pathway represents a new molecular mechanism involved in the invasion promotion in gliomas. Our findings also demonstrated that MYH9 was crucial for inducing glioma cell migration. In summary, we suggest that MYH9 is a potential molecular marker for predicting tumour progression and prognosis and highlight its role in a new molecular mechanism of tumour metastasis.
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spelling doaj-art-dc58bb61388b4ee0b67cbc94fdd2ff692025-02-09T12:30:37ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-87151-zMYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathwayZigui Chen0Chao Liu1Wei Zheng2Zhilong Li3Yuanhui Tang4Jun Peng5Changfeng Miao6Dandan Zheng7Ying Xia8Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of MedicineDepartment of Neurosurgery, Central Hospital of ZhuzhouDepartment of Neurosurgery, Central Hospital of ZhuzhouDepartment of Neurosurgery, Hunan Taihe Hospital Management Co LtdDepartment of Neurosurgery, Changsha Meixihu Sanzhen Rehabilitation HospitalDepartment of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of MedicineDepartment of Neurosurgery Second Branche, Hunan Provincial People’s Hospital (The First affiliated Hospital of Hunan Normal University)Department of Radiation Oncology, The First Affiliated Hospital Zhejiang UniversityDepartment of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of MedicineAbstract Epithelial‒mesenchymal transition (EMT) is a process in which polar epithelial cells transform into active mesenchymal cells and acquire invasion and migration capabilities (Cano CE, Motoo Y, Iovanna JL in Sci World J 10, 2010). EMT is involved in multiple physiological and pathological processes in the human body. The occurrence of EMT involves many signal transduction pathways and complex molecular mechanisms related to calnexin, growth factors, transcription factors, and the microenvironment. EMT is closely related to the invasion and metastasis of tumour cells. The MYH9 gene is closely associated with tumour progression. However, the function and regulatory mechanism of MYH9 in tumour occurrence and development remain unclear. Herein, we revealed for the first time that the migration, invasion, and metastatic abilities of glioma cells decreased significantly after MYH9 expression was downregulated. Moreover, our results suggested that MYH9 regulated the epithelial‒mesenchymal transition (EMT) process in glioma cells via β-catenin. In this mechanism, MYH9 was shown to bind to β-catenin and to increase its protein level by recruiting the deubiquitinase USP2 to form a complex. This complex suppressed β-catenin protein degradation, ultimately enhancing EMT signal transduction. This MYH9/β-catenin/EMT pathway represents a new molecular mechanism involved in the invasion promotion in gliomas. Our findings also demonstrated that MYH9 was crucial for inducing glioma cell migration. In summary, we suggest that MYH9 is a potential molecular marker for predicting tumour progression and prognosis and highlight its role in a new molecular mechanism of tumour metastasis.https://doi.org/10.1038/s41598-025-87151-zMYH9Malignantβ-cateninEpithelial-mesenchymal transition
spellingShingle Zigui Chen
Chao Liu
Wei Zheng
Zhilong Li
Yuanhui Tang
Jun Peng
Changfeng Miao
Dandan Zheng
Ying Xia
MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway
Scientific Reports
MYH9
Malignant
β-catenin
Epithelial-mesenchymal transition
title MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway
title_full MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway
title_fullStr MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway
title_full_unstemmed MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway
title_short MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway
title_sort myh9 promotes malignant progression of glioma cells through regulating β catenin stability via epithelial mesenchymal transition signaling pathway
topic MYH9
Malignant
β-catenin
Epithelial-mesenchymal transition
url https://doi.org/10.1038/s41598-025-87151-z
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