The special stemness functions of Tbx3 in stem cells and cancer development

Dong, Liang; Lyu, Xiaoming; Damola, Faleti Oluwasijibomi; He, Ming

doi:10.1016/j.semcancer.2018.09.010

Cited by 31 publications

(30 citation statements)

References 113 publications

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“…We also noted fewer and an increased number of neurospheres in YAP knockdown and overexpressing neuroblastoma cells, respectively. To further support our findings, RNA sequencing of SK-N-AS cells with YAP shRNA knockdown verses control revealed the downregulation of genes involved in mesenchymal states in other tissue types, such as JAK1 , IL6ST , and TBX3 [ 110 , 111 , 112 ].…”

Section: Yap and Its Role In High-risk Neuroblastomasupporting

confidence: 64%

A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment

Shim

Goldsmith

2021

Cancers

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Neuroblastoma is the most common extra-cranial pediatric solid tumor that accounts for more than 15% of childhood cancer-related deaths. High risk neuroblastomas that recur during or after intense multimodal therapy have a <5% chance at a second sustained remission or cure. The solid tumor microenvironment (TME) has been increasingly recognized to play a critical role in cancer progression and resistance to therapy, including in neuroblastoma. The Yes-Associated Protein (YAP) in the Hippo pathway can regulate cancer proliferation, tumor initiation, and therapy response in many cancer types and as such, its role in the TME has gained interest. In this review, we focus on YAP and its role in neuroblastoma and further describe its demonstrated and potential effects on the neuroblastoma TME. We also discuss the therapeutic strategies for inhibiting YAP in neuroblastoma.

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Section: Yap and Its Role In High-risk Neuroblastomasupporting

confidence: 64%

A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment

Shim

Goldsmith

2021

Cancers

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“…The protein encoded by TBX3 belongs to the evolutionarily conserved T-box family of transcription factors that play critical roles in early embryonic development. Overexpression of Tbx3 is associated with multiple cancers potentially by modulating cell proliferation and survival, tumor formation and metastasis, and drug resistance (46). Emerging evidence suggests that Tbx3 is not only important for stem cell self-renewal, but also is extensively involved in cancer stemness (46,47).…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of Tbx3 is associated with multiple cancers potentially by modulating cell proliferation and survival, tumor formation and metastasis, and drug resistance (46). Emerging evidence suggests that Tbx3 is not only important for stem cell self-renewal, but also is extensively involved in cancer stemness (46,47). Independent secondary signals were observed at colorectal cancer risk loci in both East-Asian populations (7,8,11,14,25) and European populations (10,13,(48)(49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians

Kweon

Cai

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background-Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians.Methods-We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians.Results-An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10 −8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10 −3 ). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10 −8 and two variants with an association near the genomewide significance level (rs60911071,

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“…Interestingly, several genes changed from protective factors to risk factors in different glioma types and vice versa. For example, TBX3 is associated with a number of cancers, including head and neck squamous cell carcinoma, gastric, breast, ovary, cervical, pancreatic, bladder, liver cancers and melanoma [25]. Its special stemness function and role as a microenvironment-dependent and epigenetically regulated lineage-commitment factor makes it a risk factor in cancers [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…For example, TBX3 is associated with a number of cancers, including head and neck squamous cell carcinoma, gastric, breast, ovary, cervical, pancreatic, bladder, liver cancers and melanoma [25]. Its special stemness function and role as a microenvironment-dependent and epigenetically regulated lineage-commitment factor makes it a risk factor in cancers [25,26]. Besides, it has been related to the hormonal therapy resistance in breast cancers [27].…”

Section: Discussionmentioning

confidence: 99%

Survival Risk Prediction Models of Gliomas Based on IDH and 1p/19q

et al. 2020

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Gliomas have been classified into different molecular subtypes based on their molecular features. To explore the prognostic factors of different subtypes of gliomas, we performed a univariate survival analysis based on the RNA-seq data of 653 patients obtained from The Cancer Genome Atlas. We identified 12205 (20.18%), 6125 (10.13%) and 5206 (8.61%) genes associated with the overall survival (OS) of the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion gliomas, respectively. Pathway enrichment analysis revealed that OS related genes were mainly involved in alcoholism, systemic lupus erythematosus, hematopoietic cell lineage and diabetes. The OS related genes were further selected using Lasso regression, and three prognostic risk score models were constructed to effectively predict the OS of the patients with different subtypes of gliomas. In total, 76 signature genes were identified and were selected to construct the three models. Moreover, neither of the 76 genes overlapped between different models, which suggested the enormous difference among the three subtypes, although some signature genes (SERPINA5, RP11.229A12.2 and RP11.62F24.2) were also identified as the OS related genes in different glioma subtypes. Interestingly, five genes (RP11.229A12.2, RP11.62F24.2, C3orf67, RP11.275H4.1 and TBX3) played opposing roles (protective or risk factor) in different subtypes. Additionally, the prognosis models consisted of a substantial proportion of non-coding RNA (58.74%, 70.13% and 58.11% in the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion). Furthermore, multivariate analysis integrating clinical variables demonstrated that risk group predicted by the prognostic models was an independent prognostic factor for gliomas. In conclusion, we have constructed and validated three models that have the potential to predict the prognosis of glioma patients. The genes and pathways identified in this study require further investigation for their underlying mechanisms and potential clinical significance in improving the OS of the glioma patients.

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The special stemness functions of Tbx3 in stem cells and cancer development

Cited by 31 publications

References 113 publications

A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment

A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment

Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians

Survival Risk Prediction Models of Gliomas Based on IDH and 1p/19q

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