Glioma cells acquire stem-like characters by extrinsic ribosome stimuli

Yuki Shirakawa, Kunimasa Ohta, Shunsuke Miyake, Ayumi Kanemaru, Akari Kuwano, Kou Yonemaru, Shota Uchino, Michiko Yamaoka, Yuki Ito, Naofumi Ito, Takuichiro Hide, Naoki Shinojima, Akitake Mukasa, Hideyuki Saito, Hirofumi Jono

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Although glioblastoma (GBM) stem-like cells (GSCs), which retain chemo-radio resistance and recurrence, are key prognostic factors in GBM patients, the molecular mechanisms of GSC development are largely unknown. Recently, several studies revealed that extrinsic ribosome incorporation into somatic cells resulted in stem cell properties and served as a key trigger and factor for the cell reprogramming process. In this study, we aimed to investigate the mechanisms underlying GSCs development by focusing on extrinsic ribosome incorporation into GBM cells. Ribosome-induced cancer cell spheroid (RICCS) formation was significantly upregulated by ribosome incorporation. RICCS showed the stem-like cell characters (number of cell spheroid, stem cell markers, and ability for trans differentiation towards adipocytes and osteocytes). In RICCS, the phosphorylation and protein expression of ribosomal protein S6 (RPS6), an intrinsic ribosomal protein, and STAT3 phosphorylation were upregulated, and involved in the regulation of cell spheroid formation. Consistent with those results, glioma-derived extrinsic ribosome also promoted GBM-RICCS formation through intrinsic RPS6 phosphorylation. Moreover, in glioma patients, RPS6 phosphorylation was dominantly observed in high-grade glioma tissues, and predominantly upregulated in GSCs niches, such as the perinecrosis niche and perivascular niche. Those results indicate the potential biological and clinical significance of extrinsic ribosomal proteins in GSC development.

Original languageEnglish
Article number2970
JournalCells
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 2021

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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