Ribosomal protein S6 promotes stem‐like characters in glioma cells

Abstract

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.

Non-stem bladder cancer cell-derived extracellular vesicles promote cancer stem cell survival in response to chemotherapy

“…Ribosomes are subcellular cytoplasmic biomolecules composed of rRNA and dozens of proteins that primarily participate in translation [ 40 , 41 ]. Recent studies have shown that ribosomes are involved in multiple biological processes, such as cellular proliferation, differentiation, homeostasis, and development of cancer [ 40 , 42 , 43 ].…”

“…Undifferentiated CSCs are known to maintain low levels of global translation and degradation activity, but they need to respond to dynamic alterations in the tumor environment during disease progression by rapidly regulating protein translational programs [ 44 – 46 ]. Maintaining the ability of CSCs to undergo self-renewal requires high translation efficiency [ 41 , 45 , 47 ], and inhibiting translation in CSCs has the potential to reduce their stem-like properties [ 48 ]. Our data revealed that EVs released by NSCCs contain cargos enriched in ribosomal proteins that could be taken up and utilized by CSCs to rapidly induce protein synthesis, enabling these cells to adapt to a dynamic tumor environment.…”

Non-Stem Bladder Cancer Cell-Derived Extracellular Vesicles Promote Cancer Stem Cell Survival in Response to Chemotherapy 

“…Undifferentiated CSCs are known to maintain low levels of global translation and degradation activity, but they need to respond to dynamic alterations in the tumor environment during disease progression by rapidly regulating protein translational programs (44)(45)(46). Maintaining the ability of CSCs to undergo self-renewal requires high translation e ciency (41,45,47), and inhibiting translation in CSCs has the potential to reduce their stem-like properties (48). Our data revealed that EVs released by NSCCs contain cargos enriched in ribosomal proteins that could be taken up and utilized by CSCs to rapidly induce protein synthesis, enabling these cells to adapt to a dynamic tumor environment.…”

Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli

“…Ito et al reported that ribosome incorporation into somatic cells depends on trypsin-activated endocytosis and ribosomes may interact with several intrinsic cell signals. Meanwhile, our recent studies revealed that ribosomal proteins are overexpressed at border niches in GBM tissues [ 15 ]. A recent study also showed that translation of ribosomal RNA and nucleolar regulation promoted glioma tumorigenesis, such as stem cell characters [ 16 ].…”

“…A recent study also showed that translation of ribosomal RNA and nucleolar regulation promoted glioma tumorigenesis, such as stem cell characters [ 16 ]. Furthermore, we also revealed that ribosome including RPS6 played crucial roles in stem-like characters in glioma cells in GBM patients [ 15 ]. However, the relationship between GSC development and ribosome incorporation as a key trigger for reprogramming is totally unknown.…”