Cancer Stem Cells in Metastasis Therapy

Çoban, Esra Aydemir; Şahın, Fikrettin

doi:10.1007/5584_2018_279

Cited by 12 publications

(8 citation statements)

References 131 publications

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“…Obtained findings showed that CSCs, similar to other stem cells being capable of self-renewal and multipotent differentiation ( Han and Oh, 2013 ), are considered as the reason behind the continuous proliferation, as well as recurrence of cancers. With the potential to initiate and sustain tumor progression, CSCs are involved in tumor progression, metastasis and therapeutic resistance in GC ( Kreso and Dick, 2014 ; Brungs et al, 2016 ; Chang, 2016 ; Çoban and Şahin, 2018 ). However, no relevant therapeutic modalities targeting CSCs have been developed yet.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Prediction Using a Stemness Index-Related Signature in a Cohort of Gastric Cancer

Chen

Zhang

Jiang

et al. 2020

Front. Mol. Biosci.

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Background With characteristic self-renewal and multipotent differentiation, cancer stem cells (CSCs) have a crucial influence on the metastasis, relapse and drug resistance of gastric cancer (GC). However, the genes that participates in the stemness of GC stem cells have not been identified. Methods The mRNA expression-based stemness index (mRNAsi) was analyzed with differential expressions in GC. The weighted gene co-expression network analysis (WGCNA) was utilized to build a co-expression network targeting differentially expressed genes (DEG) and discover mRNAsi-related modules and genes. We assessed the association between the key genes at both the transcription and protein level. Gene Expression Omnibus (GEO) database was used to validate the expression levels of the key genes. The risk model was established according to the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Furthermore, we determined the prognostic value of the model by employing Kaplan-Meier (KM) plus multivariate Cox analysis. Results GC tissues exhibited a substantially higher mRNAsi relative to the healthy non-tumor tissues. Based on WGCNA, 17 key genes (ARHGAP11A, BUB1, BUB1B, C1orf112, CENPF, KIF14, KIF15, KIF18B, KIF4A, NCAPH, PLK4, RACGAP1, RAD54L, SGO2, TPX2, TTK, and XRCC2) were identified. These key genes were clearly overexpressed in GC and validated in the GEO database. The protein-protein interaction (PPI) network as assessed by STRING indicated that the key genes were tightly connected. After LASSO analysis, a nine-gene risk model (BUB1B, NCAPH, KIF15, RAD54L, KIF18B, KIF4A, TTK, SGO2, C1orf112) was constructed. The overall survival in the high-risk group was relatively poor. The area under curve (AUC) of risk score was higher compared to that of clinicopathological characteristics. According to the multivariate Cox analysis, the nine-gene risk model was a predictor of disease outcomes in GC patients (HR, 7.606; 95% CI, 3.037–19.051; P < 0.001). We constructed a prognostic nomogram with well−fitted calibration curve based on risk score and clinical data. Conclusion The 17 mRNAsi-related key genes identified in this study could be potential treatment targets in GC treatment, considering that they can inhibit the stemness properties. The nine-gene risk model can be employed to predict the disease outcomes of the patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Prediction Using a Stemness Index-Related Signature in a Cohort of Gastric Cancer

Chen

Zhang

Jiang

et al. 2020

Front. Mol. Biosci.

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“…The study of tumor stem cells, a special class of stem celllike tumor cells, has been recently springing up vigorously. With the property of stem cell-like and resistant to chemotherapy and radiotherapy, tumor stem cells are involved in tumor multiple processes such as tumorigenesis, progression, metastasis, and recurrence after therapy [19][20][21][22]. Therefore, this study focuses on the molecular mechanisms regulating the properties of cancer stem cells.…”

Section: Discussionmentioning

confidence: 99%

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway

Wang

Zhou

et al. 2022

Aging

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Gastric cancer remains a malignant disease of the digestive tract with high mortality and morbidity worldwide. However, due to its complex pathological mechanisms and lack of effective clinical therapies, the survival rate of patients after receiving treatment is not satisfactory. An increasing number of studies have focused on cancer stem cells and their regulatory properties. In this study, we first constructed a coexpression network based on the WGCNA algorithm to identify modules with different degrees of association with tumor stemness indices. After selecting the most positively correlated modules of the stemness index, we performed a consensus clustering analysis on gastric cancer samples and constructed the co-expression network again. We then selected the modules of interest and applied univariate COX regression analysis to the genes in this module for preliminary screening. The results of the screening were then used in LASSO regression analysis to construct a risk prognostic model and subsequently a sixteen-gene model was obtained. Finally, after verifying the accuracy of the module and screening for risk genes, we identified MAGE-A3 as the final study subject. We then performed in vivo and in vitro experiments to verify its effect on tumor stemness and tumour proliferation. Our data supports that MAGE-A3 is a tumor stemness regulator and a potent prognostic biomarker which can help the prediction and treatment of gastric cancer patients.

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“…In contrast, high-grade progressive tumors often have a highly varied heterogeneous population of CSCs, perhaps due to a weakened control on asymmetric cell division as more mutations are accumulated (Khan et al, 2018). Importantly, CSCs are tightly associated with the ability to initiate metastatic tumors and are inclined to be drug resistant (Aydemir Coban and Sahin, 2018). The CSCs model is gaining scientific popularity, as the clonal model is not always applicable to the formation of human cancers and does not sufficiently clarify the differences in the level of cancer heterogeneity between grades.…”

Section: Csc Populations and Common Markersmentioning

confidence: 99%

Targeting Cancer Stem Cells by Genetically Engineered Chimeric Antigen Receptor T Cells

Alhabbab

2020

Front. Genet.

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The term cancer stem cell (CSC) starts 25 years ago with the evidence that CSC is a subpopulation of tumor cells that have renewal ability and can differentiate into several distinct linages. Therefore, CSCs play crucial role in the initiation and the maintenance of cancer. Moreover, it has been proposed throughout several studies that CSCs are behind the failure of the conventional chemo-/radiotherapy as well as cancer recurrence due to their ability to resist the therapy and their ability to re-regenerate. Thus, the need for targeted therapy to eliminate CSCs is crucial; for that reason, chimeric antigen receptor (CAR) T cells has currently been in use with high rate of success in leukemia and, to some degree, in patients with solid tumors. This review outlines the most common CSC populations and their common markers, in particular CD133, CD90, EpCAM, CD44, ALDH, and EGFR VIII , the interaction between CSCs and the immune system, CAR T cell genetic engineering and signaling, CAR T cells in targeting CSCs, and the barriers in using CAR T cells as immunotherapy to treat solid cancers.

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Cancer Stem Cells in Metastasis Therapy

Cited by 12 publications

References 131 publications

Prognostic Prediction Using a Stemness Index-Related Signature in a Cohort of Gastric Cancer

Prognostic Prediction Using a Stemness Index-Related Signature in a Cohort of Gastric Cancer

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway

Targeting Cancer Stem Cells by Genetically Engineered Chimeric Antigen Receptor T Cells

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