Caveolin-1 promotes glioma proliferation and metastasis by enhancing EMT via mediating PAI-1 activation and its correlation with immune infiltrates
Zhaoxiang Wang,
Gang Chen,
Debin Yuan,
Peizhang Wu,
Jun Guo,
Yisheng Lu,
Zhenyu Wang
Affiliations
Zhaoxiang Wang
Department of Neurosurgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China; Department of Neurosurgery, The First People's Hospital of Yancheng, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China
Gang Chen
Department of Neurosurgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China; Department of Neurosurgery, The First People's Hospital of Yancheng, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China
Debin Yuan
Department of Neurosurgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China; Department of Neurosurgery, The First People's Hospital of Yancheng, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China
Peizhang Wu
Department of Neurosurgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China; Department of Neurosurgery, The First People's Hospital of Yancheng, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China
Jun Guo
Department of Neurosurgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China; Department of Neurosurgery, The First People's Hospital of Yancheng, No. 166 Yulong West Road, Yancheng, 224000, Jiangsu, China
Yisheng Lu
Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong University, Jiangsu, 226001, China
Zhenyu Wang
Department of Pediatric General Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiaotong University, No. 355 Luding Road, Shanghai, 200062, Shanghai, China; Corresponding author.
Glioma is typically characterized by a poor prognosis and is associated with a decline in the quality of life as the disease advances. However, the development of effective therapies for glioma has been inadequate. Caveolin-1 (CAV-1) is a membrane protein that plays a role in caveolae formation and interacts with numerous signaling proteins, compartmentalizing them in caveolae and frequently exerting direct control over their activity through binding to its scaffolding domain. Although CAV-1 is a vital regulator of tumour progression, its role in glioma remains unclear. Our findings indicated that the knockdown of CAV-1 significantly inhibits the proliferation and metastasis of glioma. Subsequent mechanistic investigations demonstrated that CAV-1 promotes proliferation and metastasis by activating the photoshatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Furthermore, we demonstrated that CAV-1 overexpression upregulates the expression of serpin peptidase inhibitor, class E, member 1 (SERPINE1, also known as PAI-1), which serves as a marker for the epithelial-mesenchymal transition (EMT) process. Further research showed that PAI-1 knockdown abolished the CAV-1 mediated activation of PI3K/Akt signaling pathway. In glioma tissues, CAV-1 expression exhibited a correlation with unfavorable prognosis and immune infiltration among glioma patients. In summary, our study provided evidence that CAV-1 activates the PI3K/Akt signaling pathway by upregulating PAI-1, thereby promoting the proliferation and metastasis of glioma through enhanced epithelial-mesenchymal transition (EMT) and angiogenesis, and CAV-1 is involved in the immune infiltration.
