Role of cancer stem cells in the development of giant cell tumor of bone

War, Abdul Rouf; Dang, Kai; Jiang, Shanfen; Xiao, Zhongwei; Miao, Zhiping; Yang, Tao; Yu, Li; Qian, Airong

doi:10.1186/s12935-020-01218-7

Cited by 14 publications

(15 citation statements)

References 133 publications

(133 reference statements)

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“…It is important to note that Atxn2 -mutations were already observed to affect cholesterol homeostasis and trigger gender-dependent or hormonal effects [ 31 , 73 , 96 , 97 ]. Giant multinucleated cells can be due to increased mTOR activity [ 98 , 99 , 100 ]. Given that ATXN2 was reported to inhibit mTOR in yeast, nematodes and mice; also the absence of ATXN2L might lead to enhanced mTOR signaling and, in this way, increase the appearance of multinucleated giant cells in MEF cultures.…”

Section: Discussionmentioning

confidence: 99%

Mid-Gestation lethality of Atxn2l-Ablated Mice

Key

Harter

Sen

et al. 2020

IJMS

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Depletion of yeast/fly Ataxin-2 rescues TDP-43 overexpression toxicity. In mouse models of Amyotrophic Lateral Sclerosis via TDP-43 overexpression, depletion of its ortholog ATXN2 mitigated motor neuron degeneration and extended lifespan from 25 days to >300 days. There is another ortholog in mammals, named ATXN2L (Ataxin-2-like), which is almost uncharacterized but also functions in RNA surveillance at stress granules. We generated mice with Crispr/Cas9-mediated deletion of Atxn2l exons 5-8, studying homozygotes prenatally and heterozygotes during aging. Our novel findings indicate that ATXN2L absence triggers mid-gestational embryonic lethality, affecting female animals more strongly. Weight and development stages of homozygous mutants were reduced. Placenta phenotypes were not apparent, but brain histology showed lamination defects and apoptosis. Aged heterozygotes showed no locomotor deficits or weight loss over 12 months. Null mutants in vivo displayed compensatory efforts to maximize Atxn2l expression, which were prevented upon nutrient abundance in vitro. Mouse embryonal fibroblast cells revealed more multinucleated giant cells upon ATXN2L deficiency. In addition, in human neural cells, transcript levels of ATXN2L were induced upon starvation and glucose and amino acids exposure, but this induction was partially prevented by serum or low cholesterol administration. Neither ATXN2L depletion triggered dysregulation of ATXN2, nor a converse effect was observed. Overall, this essential role of ATXN2L for embryogenesis raises questions about its role in neurodegenerative diseases and neuroprotective therapies.

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Section: Discussionmentioning

confidence: 99%

Mid-Gestation lethality of Atxn2l-Ablated Mice

Key

Harter

Sen

et al. 2020

IJMS

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“…However, research into the methylation regulation of TGFBI in RC has not been reported. Pathway analysis also revealed that these MeDEGs were enriched in the PI3K-Akt signaling pathway, which was involved in multiple types of malignancies [46,47] , including RC [48] . In the current study, we identi ed many aberrantly methylated and expressed genes participating in the PI3K-Akt signaling pathway, which could provide a foundation for experimental research in RC.…”

Section: Discussionmentioning

confidence: 95%

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

Zhang¹,

Meng²,

Chao³

et al. 2020

Preprint

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BackgroundAbnormal hypomethylation of oncogenes and hypermethylation of tumor suppressor genes play important roles in human tumorigenesis and cancer progression, including those of rectal cancer (RC). However, conjoint analysis of RC involving both gene expression and methylation profiling datasets remains rare. This study aimed to identify methylation-regulated differentially expressed genes (MeDEGs) and to evaluate their prognostic value in RC through bioinformatics analysis.MethodsGene expression (GSE20842 and GSE68204) and gene methylation (GSE75546) profiling datasets were obtained from the Gene Expression Omnibus database. GEO2R was adopted to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs). MeDEGs were obtained by overlapping the DEGs and DMGs and then subjected to protein–protein interaction (PPI) network analysis using STRING. Modules and hub genes within the network were identified using MCODE and CytoHubba, respectively. Prognostic MeDEGs were selected by univariate Cox regression. Finally, our findings were validated based on The Cancer Genome Atlas (TCGA) database.ResultsIn total, 243 upregulated-hypomethylated and 51 downregulated-hypermethylated genes were identified as MeDEGs. A PPI network of MeDEGs was constructed with 290 nodes and 578 edges. Three modules and three hub genes—COL3A1, FPR1, and PLK1—within the network were identified. Three MeDEGs—NFE2, COMP, and LAMA1—were found to be survival-related. Furthermore, the expression and methylation status of two hub genes (excluding FPR1) and the three prognostic MeDEGs were also significantly altered in TCGA and were consistent with our findings.ConclusionsWe identified novel MeDEGs and explored their relationship with survival in RC. Our methodology may provide an effective bioinformatics basis for further understanding of the methylation-mediated regulatory mechanisms in RC.

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“…Polyploid giant tumor cells have been pathologically recognized, particularly in bones, for a long time [ 61 , 62 ], and clinical evidence has shown that the incidence and frequency of such tumor cells are significantly associated with the grade, chemoresistance, and poor prognosis of cancer patients [ 63 , 64 ]. Polyploidization is regulated by AURKA [ 65 ], AURKB [ 66 ], and c-MYC [ 67 ], followed by the degradation and inactivation of TP53, which is important for the cell cycle checkpoint.…”

Section: Tumor Regeneration After Emtmentioning

confidence: 99%

Targeting Oncoimmune Drivers of Cancer Metastasis

Kudo-Saito¹,

Ozaki²,

Imazeki³

et al. 2021

Cancers

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Residual metastasis is a major cause of cancer-associated death. Recent advances in understanding the molecular basis of the epithelial–mesenchymal transition (EMT) and the related cancer stem cells (CSCs) have revealed the landscapes of cancer metastasis and are promising contributions to clinical treatments. However, this rarely leads to practical advances in the management of cancer in clinical settings, and thus cancer metastasis is still a threat to patients. The reason for this may be the heterogeneity and complexity caused by the evolutional transformation of tumor cells through interactions with the host environment, which is composed of numerous components, including stromal cells, vascular cells, and immune cells. The reciprocal evolution further raises the possibility of successful tumor escape, resulting in a fatal prognosis for patients. To disrupt the vicious spiral of tumor–immunity aggravation, it is important to understand the entire metastatic process and the practical implementations. Here, we provide an overview of the molecular and cellular links between tumors’ biological properties and host immunity, mainly focusing on EMT and CSCs, and we also highlight therapeutic agents targeting the oncoimmune determinants driving cancer metastasis toward better practical use in the treatment of cancer patients.

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Role of cancer stem cells in the development of giant cell tumor of bone

Cited by 14 publications

References 133 publications

Mid-Gestation lethality of Atxn2l-Ablated Mice

Mid-Gestation lethality of Atxn2l-Ablated Mice

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

Targeting Oncoimmune Drivers of Cancer Metastasis

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