Sema3C Promotes the Survival and Tumorigenicity of Glioma Stem Cells through Rac1 Activation
Autor: | Wenchao Zhou, Xiaoguang Fang, Richard A. Prayson, Jeremy N. Rich, Jianghong Man, Jennifer S. Yu, Jocelyn Shoemake, Anthony Rizzo, Qiulian Wu, Shideng Bao |
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Rok vydání: | 2014 |
Předmět: |
rac1 GTP-Binding Protein
endocrine system Carcinogenesis Cell Survival Cell Adhesion Molecules Neuronal Population Gene Expression Apoptosis Mice Transgenic Nerve Tissue Proteins Receptors Cell Surface Semaphorins Biology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Paracrine signalling Cell Line Tumor Glioma medicine Animals Humans Autocrine signalling education lcsh:QH301-705.5 Cell Proliferation education.field_of_study Membrane Glycoproteins fungi Intracellular Signaling Peptides and Proteins medicine.disease Neural stem cell Cell biology Enzyme Activation lcsh:Biology (General) Cancer cell Neoplastic Stem Cells Cancer research Stem cell Glioblastoma Neoplasm Transplantation |
Zdroj: | Cell Reports, Vol 9, Iss 5, Pp 1812-1826 (2014) |
ISSN: | 2211-1247 |
Popis: | 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. |
Databáze: | OpenAIRE |
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