Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli

Autor: Kou Yonemaru, Naoki Shinojima, Kunimasa Ohta, Hideyuki Saito, Shunsuke Miyake, Hirofumi Jono, Naofumi Ito, Michiko Yamaoka, Yuki Ito, Akari Kuwano, Ayumi Kanemaru, Shota Uchino, Yuki Shirakawa, Takuichiro Hide, Akitake Mukasa
Rok vydání: 2021
Předmět:
Zdroj: Cells
Cells, Vol 10, Iss 2970, p 2970 (2021)
Volume 10
Issue 11
ISSN: 2073-4409
Popis: 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.
Databáze: OpenAIRE
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