Role of Cripto-1 during Epithelial-to-Mesenchymal Transition in Development and Cancer

Rangel, Maria Cristina; Karasawa, Hideaki; Castro, Nadia P.; Nagaoka, Tadahiro; Salomon, David; Bianco, Caterina

doi:10.1016/j.ajpath.2012.02.031

Cited by 90 publications

(106 citation statements)

References 92 publications

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“…HOTAIR can also accelerate the degradation of Ataxin-1, which can activate the promoter of E-cadherin. E-cadherin is the key regulator of the EMT, as it regulates epithelial cell-to-cell interactions (54).…”

Section: Epithelial-to-mesenchymal Transition (Emt) and Maintenance Omentioning

confidence: 99%

Long non-coding RNA HOTAIR: A novel oncogene (Review)

2015

Molecular Medicine Reports

114

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Long non-coding RNAs (lncRNAs) have been found to be pervasively transcribed in the genome and are critical regulators of the epigenome. Increasing evidence suggests that lncRNAs are aberrantly expressed in several types of human cancer and that they are important in the initiation, development and metastasis of human cancer. Previous studies have revealed that HOX transcript antisense intergenic RNA (HOTAIR) was frequently upregulated in various types of cancer, including breast cancer, esophageal cancer, lung cancer and gastric cancer. In addition, patients with high expression levels of HOTAIR have a significantly poorer prognosis, compared with those with low levels of expression. HOTAIR is involved in the control of cell apoptosis, growth, metastasis, angiogenesis, DNA repair and tumor cells metabolism. The present review provides an overview of the current knowledge concerning the role of HOTAIR in tumor development and progression.

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Section: Epithelial-to-mesenchymal Transition (Emt) and Maintenance Omentioning

confidence: 99%

Long non-coding RNA HOTAIR: A novel oncogene (Review)

2015

Molecular Medicine Reports

114

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“…Epithelial-mesenchymal transition (EMT), which was initially identified as a characteristic of morphogenesis during embryogenesis, is a transdifferentiation program that reprograms adherent epithelial cells into more phenotypical (2,18,19). Developmental genetics studies have revealed that the orchestration of EMT is critical to the development of malignant traits, such as motility, invasiveness, metastasis, dissemination and apoptosis-resistance in various tumor cells (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

TALEN-induced disruption of Nanog expression results in reduced proliferation, invasiveness and migration, increased chemosensitivity and reversal of EMT in HepG2 cells

Ding

et al. 2015

Oncology Reports

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Abstract. Accumulating evidence indicates that Nanog plays a central role in modulating the biological behaviors of human hepatocellular carcinoma (HCC). However, the underlying mechanisms remain unclear. In the present study, we employed transcription activator-like effector nucleases (TALEN) to disrupt Nanog expression in HepG2 cells and obtained subcloned cells with diallelic Nanog mutations. Significantly, we found that the expression of pluripotency factors Sox2, Oct4 and Klf4, as well as expression of cancer stem cell (CSC) marker CD133, in the Nanog-targeted HepG2 cells was markedly downregulated. This finding suggests that Nanog may play an important role in maintaining the pluripotency and malignancy of HepG2 cells. We also revealed that Nanog regulated cell proliferation by modulating the expression of cyclin D1/D3/E1 and CDK2, respectively. Additionally, the disruption of Nanog resulted in the downregulation of epithelial-mesenchymal transition (EMT) regulators Snail and Twist, which contributed to the elevated level of epithelial marker E-cadherin, and to the decreased level of mesenchymal markers N-cadherin and vimentin in the HepG2 cells. In addition, the Nanog-targeted HepG2 cells exhibited reduced ability of invasion, migration and chemoresistance in vitro. In conclusion, the disruption of Nanog expression results in less proliferation, invasiveness, migration, more chemosensitivity and reversal of EMT in HepG2 cells, by which Nanog plays crucial roles in influencing the malignant phenotype of HepG2 cells. IntroductionHuman hepatocellular carcinoma (HCC) is considered as the third leading cause of cancer-related death worldwide (1-3). In recent years, although surgical treatment has greatly improved the survival rate of HCC patients, its prognosis and survival rate remain poor due to frequent intra-hepatic and extrahepatic metastases and dissemination (3,4). Consequently, further investigation of the underlying molecular mechanisms are vital to identify novel therapeutic interventions and to improve the prognosis for HCC.Nanog, a central transcription regulator required for maintaining the self-renewal capacity and pluripotent state of embryonic stem cells (ESCs) along with Oct4 and Sox2 (5-10), exhibits elevated expression in various types of tumor cells (11,12). Intensive studies indicate that Nanog also executes parallel functions as in ESCs, participating in tumorigenesis and promoting the progression of certain types of tumors, including pancreatic cancer, gastrointestinal tumors, breast cancer, head and neck squamous cell carcinomas and human HCC (13-16). In addition, our previous study was the first to demonstrate that Nanog is involved in the invasion, chemoresistance, clonogenicity, migration and metastasis of the cervical carcinoma HeLa cell line (17). Nevertheless, the precise role of Nanog in human HCC has not been fully explored.Epithelial-mesenchymal transition (EMT), which was initially identified as a characteristic of morphogenesis during embryogenesis, is a transdifferentiation ...

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“…In Fig. 3, the immunoblot assay shows expression levels of downstream molecules of brachyury, such as E-cadherin [46] and p-ERK [47], were elevated (day 6). ERK and β -actin were used as controls for protein quantification.…”

Section: Resultsmentioning

confidence: 99%

BTNET : boosted tree based gene regulatory network inference algorithm using time-course measurement data

Park

Kim²,

Shin

et al. 2018

BMC Syst Biol

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BackgroundIdentifying gene regulatory networks is an important task for understanding biological systems. Time-course measurement data became a valuable resource for inferring gene regulatory networks. Various methods have been presented for reconstructing the networks from time-course measurement data. However, existing methods have been validated on only a limited number of benchmark datasets, and rarely verified on real biological systems.ResultsWe first integrated benchmark time-course gene expression datasets from previous studies and reassessed the baseline methods. We observed that GENIE3-time, a tree-based ensemble method, achieved the best performance among the baselines. In this study, we introduce BTNET, a boosted tree based gene regulatory network inference algorithm which improves the state-of-the-art. We quantitatively validated BTNET on the integrated benchmark dataset. The AUROC and AUPR scores of BTNET were higher than those of the baselines. We also qualitatively validated the results of BTNET through an experiment on neuroblastoma cells treated with an antidepressant. The inferred regulatory network from BTNET showed that brachyury, a transcription factor, was regulated by fluoxetine, an antidepressant, which was verified by the expression of its downstream genes.ConclusionsWe present BTENT that infers a GRN from time-course measurement data using boosting algorithms. Our model achieved the highest AUROC and AUPR scores on the integrated benchmark dataset. We further validated BTNET qualitatively through a wet-lab experiment and showed that BTNET can produce biologically meaningful results.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0547-0) contains supplementary material, which is available to authorized users.

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Role of Cripto-1 during Epithelial-to-Mesenchymal Transition in Development and Cancer

Cited by 90 publications

References 92 publications

Long non-coding RNA HOTAIR: A novel oncogene (Review)

Long non-coding RNA HOTAIR: A novel oncogene (Review)

TALEN-induced disruption of Nanog expression results in reduced proliferation, invasiveness and migration, increased chemosensitivity and reversal of EMT in HepG2 cells

BTNET : boosted tree based gene regulatory network inference algorithm using time-course measurement data

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