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Cited by 478Glioma Diagnosis and TreatmentCancer Cells and MetastasisCytokine Signaling Pathways and Interactions

STAT3 Is Required for Proliferation and Maintenance of Multipotency in Glioblastoma Stem Cells

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Sherry, Maureen M., Reeves, Andrew, Wu, Julian K., Cochran, Brent H.·2009·Stem Cells
DOI 10.1002/stem.185PMC PMC4391626
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Abstract

Signal transducer and activator of transcription 3 (STAT3) regulates diverse cellular processes, including cell growth, differentiation, and apoptosis, and is frequently activated during tumorigenesis. Recently, putative glioblastoma stem cells (GBM-SCs) were isolated and characterized. These cells can self-renew indefinitely in culture, are highly tumorigenic, and retain the ability to differentiate in culture. We have found that treatment of GBM-SCs with two chemically distinct small molecule inhibitors of STAT3 DNA-binding inhibits cell proliferation and the formation of new neurospheres from single cells. Genetic knockdown of STAT3 using a short hairpin RNA also inhibits GBM-SC proliferation and neurosphere formation, confirming that these effects are specific to STAT3. Although STAT3 inhibition can induce apoptosis in serum-derived GBM cell lines, this effect was not observed in GBM-SCs grown in stem cell medium. Markers of neural stem cell multipotency also decrease upon STAT3 inhibition, suggesting that STAT3 is required for maintenance of the stem-like characteristics of these cells. Strikingly, even a transient inhibition of STAT3 leads to irreversible growth arrest and inhibition of neurosphere formation. These data suggest that STAT3 regulates the growth and self-renewal of GBM-SCs and is thus a potential target for cancer stem cell-directed therapy of glioblastoma multiforme.

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  • STAT3 is involved in inflammation-associated carcinogenesis, suppression of the antitumor immune response, and maintenance of cancer stem cells.

    “STAT3 is also involved in inflammation-associated carcinogenesis, suppression of the antitumor immune response, and maintenance of cancer stem cells.”

    From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [98]

    The Discussion (page unavailable) reports that inhibiting STAT3 causes glioblastoma stem cells to lose self-renewal potential, supporting the cancer-stem-cell component. It also discusses STAT3 in tumor formation, but does not establish the more specific claim of inflammation-associated carcinogenesis. No passage found supports suppression of the antitumor immune response. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Genetic or pharmacologic inhibition of STAT3 in glioblastoma stem cells, even transiently, leads to a loss of multipotency and an irreversible growth arrest.

    “In addition, genetic or pharmacologic inhibition of STAT3 in glioblastoma stem cells, even transiently, leads to a loss of multipotency and an irreversible growth arrest, suggesting that STAT3 is required for maintenance and proliferation of cancer stem cells in this system.98”

    From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [98]

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Authors
Sherry, M. M., Reeves, A., Wu, J. K., & Cochran, B. H.
Affiliations
  • Department of Physiology, Tufts University, Boston, Massachusetts, USA
  • Tufts University (US)
  • Tufts Medical Center (US)
Corresponding author
Cochran, Brent H.
ORCID
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2009-08-05
Volume
27
Issue
10
Pages
2383-2392
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1002/stem.185
PMC
PMC4391626
OpenAlex
W2062165914
Cited by
478
References
3
Citations by year
2026: 16 · 2025: 8 · 2024: 12 · 2023: 28 · 2022: 25 · 2021: 33 · 2020: 34 · 2019: 35 · 2018: 23 · 2017: 34 · 2016: 26 · 2015: 31 · 2014: 38 · 2013: 47 · 2012: 28
FWCI
13.97
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Stem Cells (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Brain Tumor Society
  • Catherine Pappas
  • NIH training grant (T32 DK07542)
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
STAT3, glioblastoma stem cells, glioblastoma, cell proliferation, self-renewal, multipotency, neurosphere formation, STAT3 inhibitor, apoptosis, cancer stem cell therapy, shRNA knockdown
MeSH terms
Aged, 80 and over, Brain Neoplasms, Culture Media, Female, Glioblastoma, Growth Inhibitors, Humans, Male, Neoplastic Stem Cells, Down-Regulation, Spheroids, Cellular, RNA Interference, Multipotent Stem Cells, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Inhibitor of Differentiation Protein 1

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