Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli
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 c...
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2021
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oai:doaj.org-article:04990f342bea47d793822790bc2772e92021-11-25T17:09:54ZGlioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli10.3390/cells101129702073-4409https://doaj.org/article/04990f342bea47d793822790bc2772e92021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2970https://doaj.org/toc/2073-4409Although 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.Yuki ShirakawaKunimasa OhtaShunsuke MiyakeAyumi KanemaruAkari KuwanoKou YonemaruShota UchinoMichiko YamaokaYuki ItoNaofumi ItoTakuichiro HideNaoki ShinojimaAkitake MukasaHideyuki SaitoHirofumi JonoMDPI AGarticleglioblastomaribosomeribosomal protein S6ribosome-induced cancer cell spheroidBiology (General)QH301-705.5ENCells, Vol 10, Iss 2970, p 2970 (2021) |
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glioblastoma ribosome ribosomal protein S6 ribosome-induced cancer cell spheroid Biology (General) QH301-705.5 |
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glioblastoma ribosome ribosomal protein S6 ribosome-induced cancer cell spheroid Biology (General) QH301-705.5 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 Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Yuki Shirakawa |
| title |
Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli |
| title_short |
Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli |
| title_full |
Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli |
| title_fullStr |
Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli |
| title_full_unstemmed |
Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli |
| title_sort |
glioma cells acquire stem-like characters by extrinsic ribosome stimuli |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/04990f342bea47d793822790bc2772e9 |
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