Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation
Summary: Different cancer cell compartments often communicate through soluble factors to facilitate tumor growth. Glioma stem cells (GSCs) are a subset of tumor cells that resist standard therapy to contribute to disease progression. How GSCs employ a distinct secretory program to communicate with a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714009243 |
| _version_ | 1819157849033408512 |
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| author | Jianghong Man Jocelyn Shoemake Wenchao Zhou Xiaoguang Fang Qiulian Wu Anthony Rizzo Richard Prayson Shideng Bao Jeremy N. Rich Jennifer S. Yu |
| author_facet | Jianghong Man Jocelyn Shoemake Wenchao Zhou Xiaoguang Fang Qiulian Wu Anthony Rizzo Richard Prayson Shideng Bao Jeremy N. Rich Jennifer S. Yu |
| author_sort | Jianghong Man |
| collection | DOAJ |
| description | Summary: Different cancer cell compartments often communicate through soluble factors to facilitate tumor growth. Glioma stem cells (GSCs) are a subset of tumor cells that resist standard therapy to contribute to disease progression. How GSCs employ a distinct secretory program to communicate with and nurture each other over the nonstem tumor cell (NSTC) population is not well defined. Here, we show that GSCs preferentially secrete Sema3C and coordinately express PlexinA2/D1 receptors to activate Rac1/nuclear factor (NF)-κB signaling in an autocrine/paracrine loop to promote their own survival. Importantly, Sema3C is not expressed in neural progenitor cells (NPCs) or NSTCs. Disruption of Sema3C induced apoptosis of GSCs, but not NPCs or NSTCs, and suppressed tumor growth in orthotopic models of glioblastoma. Introduction of activated Rac1 rescued the Sema3C knockdown phenotype in vivo. Our study supports the targeting of Sema3C to break this GSC-specific autocrine/paracrine loop in order to improve glioblastoma treatment, potentially with a high therapeutic index. : Glioma stem cells (GSCs) have a high capacity for self-renewal, invasion, and survival. How they communicate with each other to survive and maintain their identity is not clear. Man et al. now show that GSCs have co-opted a neurodevelopmental program to activate Rac1 to promote defining features of GSCs. |
| first_indexed | 2024-12-22T16:15:18Z |
| format | Article |
| id | doaj.art-2083a50321224e64bca9da501aa446ba |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T16:15:18Z |
| publishDate | 2014-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2083a50321224e64bca9da501aa446ba2022-12-21T18:20:22ZengElsevierCell Reports2211-12472014-12-019518121826Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 ActivationJianghong Man0Jocelyn Shoemake1Wenchao Zhou2Xiaoguang Fang3Qiulian Wu4Anthony Rizzo5Richard Prayson6Shideng Bao7Jeremy N. Rich8Jennifer S. Yu9Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Anatomic Pathology, Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Corresponding authorSummary: Different cancer cell compartments often communicate through soluble factors to facilitate tumor growth. Glioma stem cells (GSCs) are a subset of tumor cells that resist standard therapy to contribute to disease progression. How GSCs employ a distinct secretory program to communicate with and nurture each other over the nonstem tumor cell (NSTC) population is not well defined. Here, we show that GSCs preferentially secrete Sema3C and coordinately express PlexinA2/D1 receptors to activate Rac1/nuclear factor (NF)-κB signaling in an autocrine/paracrine loop to promote their own survival. Importantly, Sema3C is not expressed in neural progenitor cells (NPCs) or NSTCs. Disruption of Sema3C induced apoptosis of GSCs, but not NPCs or NSTCs, and suppressed tumor growth in orthotopic models of glioblastoma. Introduction of activated Rac1 rescued the Sema3C knockdown phenotype in vivo. Our study supports the targeting of Sema3C to break this GSC-specific autocrine/paracrine loop in order to improve glioblastoma treatment, potentially with a high therapeutic index. : Glioma stem cells (GSCs) have a high capacity for self-renewal, invasion, and survival. How they communicate with each other to survive and maintain their identity is not clear. Man et al. now show that GSCs have co-opted a neurodevelopmental program to activate Rac1 to promote defining features of GSCs.http://www.sciencedirect.com/science/article/pii/S2211124714009243 |
| spellingShingle | Jianghong Man Jocelyn Shoemake Wenchao Zhou Xiaoguang Fang Qiulian Wu Anthony Rizzo Richard Prayson Shideng Bao Jeremy N. Rich Jennifer S. Yu Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation Cell Reports |
| title | Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation |
| title_full | Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation |
| title_fullStr | Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation |
| title_full_unstemmed | Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation |
| title_short | Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation |
| title_sort | sema3c promotes the survival and tumorigenicity of glioma stem cells through rac1 activation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714009243 |
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