CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance
Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared...
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Published in | Stem cell reports Vol. 8; no. 1; pp. 140 - 151 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
10.01.2017
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, we found that CD59 was upregulated to protect CSCs from complement-dependent cytotoxicity. CD59 silencing significantly enhanced complement destruction and completely suppressed tumorigenesis in CSC-xenografted nude mice. Furthermore, we identified that SOX2 upregulates CD59 in epithelial CSCs. In addition, we revealed that SOX2 regulates the transcription of mCd59b, leading to selective mCD59b abundance in murine testis spermatogonial stem cells. Therefore, we demonstrated that CD59 regulation by SOX2 is required for stem cell evasion of complement surveillance. This finding highlights the importance of complement surveillance in eliminating CSCs and may suggest CD59 as a potential target for cancer therapy.
•CD59 upregulation is required for stem cells evading complement surveillance•SOX2 is responsible for CD59 upregulation in stem cells•SOX2 regulates mCD59b selective expression in testis spermatogonial stem cells
CD59 and mCD59b in mouse, but not other membrane regulatory proteins, are upregulated by SOX2 in stem cells and are required to evade complement surveillance. CD59 insufficiency may result in near-complete arrest of tumor growth and loss of tumorigenesis of cancer stem cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2213-6711 2213-6711 |
DOI: | 10.1016/j.stemcr.2016.11.008 |