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Cancer Res. 2017 Oct 1;77(19):5360-5373. doi: 10.1158/0008-5472.CAN-17-1294. Epub 2017 Aug 14.

S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma.

Author information

1
The Jackson Laboratory, Bar Harbor, Maine.
2
Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida.
3
Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
4
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida.
5
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Neuroscience and Aging Laboratory, School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts.
7
Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
8
The Jackson Laboratory, Bar Harbor, Maine. kyun@houstonmethodist.org.
9
Kenneth R. Peak Brain and Pituitary Tumor Center, Department of Neurosurgery, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas.

Abstract

Glioma stem cells (GSC) and epithelial-mesenchymal transition (EMT) are strongly associated with therapy resistance and tumor recurrence, but the underlying mechanisms are incompletely understood. Here, we show that S100A4 is a novel biomarker of GSCs. S100A4+ cells in gliomas are enriched with cancer cells that have tumor-initiating and sphere-forming abilities, with the majority located in perivascular niches where GSCs are found. Selective ablation of S100A4-expressing cells was sufficient to block tumor growth in vitro and in vivo We also identified S100A4 as a critical regulator of GSC self-renewal in mouse and patient-derived glioma tumorspheres. In contrast with previous reports of S100A4 as a reporter of EMT, we discovered that S100A4 is an upstream regulator of the master EMT regulators SNAIL2 and ZEB along with other mesenchymal transition regulators in glioblastoma. Overall, our results establish S100A4 as a central node in a molecular network that controls stemness and EMT in glioblastoma, suggesting S100A4 as a candidate therapeutic target. Cancer Res; 77(19); 5360-73. ©2017 AACR.

PMID:
28807938
PMCID:
PMC5626628
DOI:
10.1158/0008-5472.CAN-17-1294
[Indexed for MEDLINE]
Free PMC Article

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