Ribosomal protein S6 promotes stem-like characters in glioma cells.


Journal

Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776

Informations de publication

Date de publication:
Jun 2020
Historique:
received: 10 12 2019
revised: 18 03 2020
accepted: 20 03 2020
pubmed: 5 4 2020
medline: 20 6 2020
entrez: 5 4 2020
Statut: ppublish

Résumé

Glioblastoma multiforme (GBM), a lethal brain tumor developing in the white matter of the adult brain, contains a small population of GBM stem cells (GSCs), which potentially cause chemotherapeutic resistance and tumor recurrence. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. A recent study reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans-differentiation toward multipotency. This study aimed to investigate the mechanism underlying stemness acquisition in GBM cells by focusing on 40S ribosomal protein S6 (RPS6). RPS6 was significantly upregulated in high-grade glioma and localized at perivascular, perinecrotic, and border niches in GBM tissues. siRNA-mediated RPS6 knock-down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and GSC marker expression; STAT3 was downregulated in GBM cells. RPS6 overexpression enhanced the tumorsphere potential of GSCs and these effects were attenuated by STAT3 inhibitor (AG490). Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data herein indicated that RPS6 was predominant in GSC niches, concurrent with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC-predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemoradioresistance and GBM recurrence.

Identifiants

pubmed: 32246865
doi: 10.1111/cas.14399
pmc: PMC7293102
doi:

Substances chimiques

Ribosomal Protein S6 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2041-2051

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 18H02591
Organisme : Japan Society for the Promotion of Science
ID : 26713006

Informations de copyright

© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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Auteurs

Yuki Shirakawa (Y)

Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.

Takuichiro Hide (T)

Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Japan.

Michiko Yamaoka (M)

Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.

Yuki Ito (Y)

Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.

Naofumi Ito (N)

Department of Developmental Neurobiology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.

Kunimasa Ohta (K)

Department of Developmental Neurobiology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.

Naoki Shinojima (N)

Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Akitake Mukasa (A)

Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Hideyuki Saito (H)

Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Pharmacy, Kumamoto University Hospital, Kumamoto City, Japan.

Hirofumi Jono (H)

Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Pharmacy, Kumamoto University Hospital, Kumamoto City, Japan.

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