CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma

Chen, Du-Chu; Liang, Youde; Peng, Liang; Wang, Yi–Ze; Ai, Chun-Zhi; Zhu, Xinxing; Yan, Ya-Wei; Saeed, Yasmeen; Yu, Bin; Huang, Jingying; Gao, Yuxin; Liu, Jiaqi; Jiang, Yi‐Zhou; Liu, Min; Chen, Demeng

doi:10.1186/s12935-017-0473-z

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…Knocking-down of CBFA2T2 can inhibit cell migration and invasion in RCC cells in vitro, and reduce ALDH high cancer stem cells (CSCs) populations. CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines 35 , 36 . CBFA2T2 is required for tumorigenesis in the murine colitis-associated carcinoma 37 - 39 .…”

Section: Discussionmentioning

confidence: 99%

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

et al. 2020

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Purpose: Our study is designed to develop and certify a promising prognostic signature for hepatocellular carcinoma (HCC). Materials and methods: We retrospectively analyzed mRNA expression profiles and clinicopathological data fetched from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. We formulated a prognostic seven-gene signature composed of differentially expressed mRNAs (DEmRNAs) between HCC and nonneoplastic tissues through univariate Cox regression analysis. The receiver operating characteristic (ROC) curve, survival analysis and multivariate Cox regression analysis as well as nomograms were utilized to assess the prognostic performance of the seven-gene signature. Results: The risk score based on a seven-gene signature categorized HCC subjects into a high-and low-risk group. There was significantly discrepant overall survival (OS) between patients in both groups and the corresponding ROC curve revealed a satisfactory predictive performance in HCC survival in both TCGA and GSE76427 cohort. Multivariate Cox regression analysis demonstrated that a seven-gene signature was an independently prognostic factor for HCC. Nomograms combining this prognostic signature with significant clinical characteristics conferred a crucial reference to predict the 1-,3-and 5 years OS. Conclusions: Our study defined a promising seven-gene signature and nomogram model to forecast the OS of HCC patients, which is instrumental in clinical decision and personalized therapy.

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Section: Discussionmentioning

confidence: 99%

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

et al. 2020

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“…High ALDH1 expression in RCC confers stem cell properties such as sphere-forming capacity in vitro 49 . ALDH1 gene expression has also been correlated with tumor grade but not tumor stage in patients with RCC 50 . Overall pooled analysis suggests that high expression of CSC markers (including CD133, CD44, CXCR4, and CD105) predicts poor overall survival, cancer-specific survival, disease-free survival, and progression-free survival 50 .…”

Section: Discussionmentioning

confidence: 99%

“…ALDH1 gene expression has also been correlated with tumor grade but not tumor stage in patients with RCC 50 . Overall pooled analysis suggests that high expression of CSC markers (including CD133, CD44, CXCR4, and CD105) predicts poor overall survival, cancer-specific survival, disease-free survival, and progression-free survival 50 . However, the molecular mechanism connecting ALDH1 and stem cells in RCC remains to be fully explored.…”

Section: Discussionmentioning

confidence: 99%

Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts

Bhasin

Khanna

et al. 2019

Oncogenesis

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Several therapeutic options are available for metastatic RCC, but responses are almost never complete, and resistance to therapy develops in the vast majority of patients. Consequently, novel treatments are needed to combat resistance to current therapies and to improve patient outcomes. We have applied integrated transcriptome and proteome analyses to identify cathepsin B (CTSB), a cysteine proteinase of the papain family, as one of the most highly upregulated gene products in established human RCC xenograft models of resistance to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). We used established RCC models to test the significance of CTSB in the progression of renal cancer. Our evaluation of CTSB showed that stable CTSB knockdown suppressed RCC growth in vitro and in vivo. Stable over-overexpression of wild-type CTSB (CTSBwt/hi), but not of an CTSB active site mutant (CTSBN298A), rescued cell growth in CTSB knockdown cells and abolished the efficacy of VEGFR TKI treatment. Genome-wide transcriptome profiling of CTSB knockdown cells demonstrated significant effects on multiple metabolic and stem cell-related pathways, with ALDHA1A (ALDH1) as one of the most significantly downregulated genes. Importantly, survival analysis across 16 major TCGA cancers revealed that CTSB overexpression is associated with low rates of three and five year patient survival rates (P = 2.5e–08, HR = 1.4). These data strongly support a contribution of CTSB activity to RCC cell growth and tumorigenicity. They further highlight the promise of CTSB inhibition in development of novel combination therapies designed to improve efficacy of current TKI treatments of metastatic RCC.

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“…CD105 + cells derived from RCCs were enriched in tumor-initiating stem cells that expressed stem cell markers. Renal CSCs have been frequently identified by use of stem cell markers such as CD133 and CD44 (19,37) and by use of several functional methods including the sphere-formation assay and ALDH activity (15,(38)(39)(40). However, there are contradicting reports on CSC markers and functional analysis.…”

Section: -Year Metastasis and Recurrence-free Survival Curves Of Patients With Clear-cell Renal Cell Carcinoma (Ccrcc) According To Tumormentioning

confidence: 99%

COMMD5 Inhibits Malignant Behavior of Renal Cancer Cells

et al. 2021

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Background/Aim: Copper metabolism MURR1 domain-containing 5 (COMMD5) is mainly expressed in renal tubules (RTs), where it facilitates re-differentiation of injured RTs. We reported that COMMD5 regulates the expression of epidermal growth factor receptor by participating in its endocytic membrane trafficking, thus inhibiting tumor growth.Here we aimed to determine the role of COMMD5 in malignant phenotypes of renal cell carcinoma (RCC). Materials and Methods: The associations between COMMD5 levels in RTs adjacent to RCC tumors in patients and their clinicopathologic characteristics were evaluated, and the effects of COMMD5 on cancer stemness in RCC cells were investigated. Results: Low COMMD5 levels in RTs correlated with high tumorigenesis and poor patient outcomes. COMMD5 overexpression in RCC cells reduced the proportion of cancer stem cell-like cells and their malignant phenotypes, including proliferation, invasion and sphere formation. Secreted COMMD5 from RT cells also reduced malignant phenotypes. Conclusion: COMMD5 might suppress malignant phenotypes of RCC, thus inhibiting tumor development and improving patient prognosis.Copper metabolism MURR1 domain-containing 5 (COMMD5), also known as hypertension-related, calcium-regulated gene, is characterized by a conserved COMM domain at its carboxyterminal end (1). Its expression is higher in the parathyroid and kidney of spontaneously hypertensive rats than in normotensive rats (2). Functional studies indicated that COMMD5 overexpression in kidney cells facilitates their differentiation, with a lower proliferative capacity (3). Overexpression of COMMD5 in proximal renal tubules (RTs) of mice accelerated tubular repair after acute kidney injury by facilitating redifferentiation of injured RT cells through the induction of P21 CIP1/WAF1 via a p53-independent pathway, resulting in faster recovery of renal function and a superior survival rate (4).Cancer afflicted about 18.1 million new patients worldwide in 2018 and accounted for nearly 9.6 million related deaths (5). Cancer morbidity and mortality are rapidly growing in every region of the world. The high mortality rate often correlates with a lack of clear symptoms, which results in late diagnosis for patients and the development of cancer resistant to chemotherapy and radiotherapy. Recent progress in cancer research has revealed that the presence of cancer stem cells (CSCs) is pivotal for the development of malignant phenotypes of various cancer types, including invasion, metastasis, recurrence and resistance to therapy (6-8). CSCs are small populations of cells that have the potential to reproduce and sustain cancer and the abilities of multiple differentiation and self-renewal (9, 10).Malignant kidney cancers afflict about 350,000 new patients worldwide, and the incidence of renal cell carcinoma (RCC) is increasing annually (11,12). Advanced kidney cancer in adults is resistant to conventional chemotherapy 2805 This article is freely accessible online.

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CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma

Cited by 7 publications

References 30 publications

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts

COMMD5 Inhibits Malignant Behavior of Renal Cancer Cells

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