KLF4 is a tumor suppressor in anaplastic meningioma stem-like cells and human rneningiomas
Meningiomas are the most common primary tumors in central nervous system. While recent studies have revealed genetic clues to lower grade human meningiomas, the molecular determinants driving the progression and recurrence of anaplastic meningi- oma, the most malignant subtype with a low prevalence...
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| Published in | 分子细胞生物学报：英文版 Vol. 9; no. 4; pp. 315 - 324 |
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| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
2017
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Meningiomas are the most common primary tumors in central nervous system. While recent studies have revealed genetic clues to lower grade human meningiomas, the molecular determinants driving the progression and recurrence of anaplastic meningi- oma, the most malignant subtype with a low prevalence but high morbidity, are still poorly understood. It has been proposed that high recurrence rates of malignant meningiomas are linked to cancer stem cells. Indeed, tumor stem-Uke cells have been iso- lated from various meningioma subtypes, but never been obtained from anaplastic meningioma, in this study, we successfully isolated stem-Uke cells from human anaplastic meningioma. These cells are capable of forming spheres and initiating xenograft tumors that recapitulate anaplastic meningioma phenotypes, and thus could serve as an in vitro model for malignant meningi- omas. KLF4, a transcription factor known for its role in sternness maintenance, was identified as one of the most frequently mutated genes in the benign secretory meningioma. Interestingly, we found that KLF4 is downregulated in anaplastic meningi- oma compared with low-grade meningioma subtypes. By manipulating KLF4 expression in anaplastic meningioma stem-like cells, we demonstrated that KLF4 acts as a tumor suppressor during malignant progression in meningioma, affecting apoptosis, prolif- eration, invasion, and cell cycle. These results suggest a potential therapeutic value of KLF4 for clinical intervention of anaplastic meningioma. |
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| Bibliography: | 31-2002/Q Meningiomas are the most common primary tumors in central nervous system. While recent studies have revealed genetic clues to lower grade human meningiomas, the molecular determinants driving the progression and recurrence of anaplastic meningi- oma, the most malignant subtype with a low prevalence but high morbidity, are still poorly understood. It has been proposed that high recurrence rates of malignant meningiomas are linked to cancer stem cells. Indeed, tumor stem-Uke cells have been iso- lated from various meningioma subtypes, but never been obtained from anaplastic meningioma, in this study, we successfully isolated stem-Uke cells from human anaplastic meningioma. These cells are capable of forming spheres and initiating xenograft tumors that recapitulate anaplastic meningioma phenotypes, and thus could serve as an in vitro model for malignant meningi- omas. KLF4, a transcription factor known for its role in sternness maintenance, was identified as one of the most frequently mutated genes in the benign secretory meningioma. Interestingly, we found that KLF4 is downregulated in anaplastic meningi- oma compared with low-grade meningioma subtypes. By manipulating KLF4 expression in anaplastic meningioma stem-like cells, we demonstrated that KLF4 acts as a tumor suppressor during malignant progression in meningioma, affecting apoptosis, prolif- eration, invasion, and cell cycle. These results suggest a potential therapeutic value of KLF4 for clinical intervention of anaplastic meningioma. anaplastic meningioma, KLF4, tumor suppressor, cancer stem-like cells, stemness maintenance |
| ISSN: | 1674-2788 1759-4685 |