Epithelial-to-mesenchymal transition–related transcription factors are up-regulated in ependymomas and correlate with a poor prognosis

Malgulwar, Prit Benny; Nambirajan, Aruna; Pathak, Pankaj; Rajeshwari, Madhu; Suri, Vaishali; Sarkar, Chitra; Singh, Manmohan; Sharma, Mehar Chand

doi:10.1016/j.humpath.2018.07.018

Cited by 26 publications

(20 citation statements)

References 32 publications

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“…alleninstitute.org) (FC = 49.7) (Figure 2F). Collectively, these data suggest that MECs are undergoing epithelial-mesenchymal transition (EMT), a phenotype that has recently been described in PFA (Malgulwar et al, 2018) as a response to hypoxic stress, which is also inferred by the presence of necrosis commonly seen in PFA tumors.…”

Section: Resultsmentioning

confidence: 52%

Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology

et al. 2020

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Section: Resultsmentioning

confidence: 52%

Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology

et al. 2020

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“…In cancer, the process of EMT confers enhanced metastatic potential, increases stem cell-like characteristics, inhibits apoptosis and aids in immune escape, all of which are fundamental events in tumor progression [ 9 – 13 ]. The cardinal EMT regulating transcription factors (TFs): Snail and Slug have been found to be upregulated in various cancers [ 14 – 22 ], including ependymomas [ 23 ]. However, the mechanisms by which Snail and Slug contribute to the pathogenesis and aggressiveness of these tumors are largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional co-expression regulatory network analysis for Snail and Slug identifiesIL1R1, an inflammatory cytokine receptor, to be preferentially expressed in ST-EPN-RELAand PF-EPN-A molecular subgroups of intracranial ependymomas

et al. 2018

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Recent molecular subgrouping of ependymomas (EPN) by DNA methylation profiling has identified ST-EPN-RELA and PF-EPN-A subgroups to be associated with poor outcome. Snail/Slug are cardinal epithelial-to-mesenchymal transcription factors (EMT-TFs) and are overexpressed in several CNS tumors, including EPNs. A systematic analysis of gene-sets/modules co-expressed with Snail and Slug genes using published expression microarray dataset (GSE27279)identified 634 genes for Snail with enriched TGF-β, PPAR and PI3K signaling pathways, and 757 genes for Slug with enriched focal adhesion, ECM-receptor interaction and regulation of actin cytoskeleton related pathways. Of 37 genes commonly expressed with both Snail and Slug, IL1R1, a cytokine receptor of interleukin-1 receptor family, was positively correlated with Snail (r=0.43) and Slug (r=0.51), preferentially expressed in ST-EPN-RELA and PF-EPN-A molecular groups, and enriched for pathways related to inflammation, angiogenesis and glycolysis. IL1R1 expression was fairly specific to EPNs among various CNS tumors analyzed. It also showed significant positive correlation with EMT, stemness and MDSC (myeloid derived suppressor cell) markers. Our study reports IL1R1 as a poor prognostic marker associated with EMT-like phenotype and stemness in EPNs. Our findings emphasize the need to further examine and validate IL1R1 as a novel therapeutic target in aggressive subsets of intracranial EPNs.

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“…4A). Previous studies have reported that the TFs, including SNAI1, SNAI2, ZEB1, ZEB2, TWIST1 and TWIST2, can simultaneously regulate the expression of E-cadherin and N-cadherin (47). After the respective siRNAs were used to knock down the expression levels of these TFs aforementioned in A2780 cells, the mRNA expression levels of N-cadherin were downregulated by differing degrees in all siRNAs tested compared with those in cells transfected with siCtrl (Fig.…”

Section: Bap31 Regulates the Expression Of E-cadherin And N-cadherin On A Transcriptional Levelmentioning

confidence: 81%

B‑cell receptor‑associated protein 31 promotes migration and invasion in ovarian cancer cells

et al. 2021

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B cell receptor associated protein 31 (BAP31) is a member of the B cell receptor that functions as a transporter for numerous types of newly formed proteins from the endoplasmic reticulum to the Golgi apparatus. Previous studies found that that BAP31 serves an important role in the pathogenesis of malignancy but its specific effect on ovarian cancer is not clear. The present study aimed to investigate whether BAP31 affects ovarian cancer and its underlying mechanism. In the present study, ovarian cancer tissue, human ovarian normal epithelial cell line IOSE80 and five ovarian cancer cell lines (A2780, Hey-T30, COC1, SKOV3 and OVCAR3) underwent reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8, Transwell and co-immunoprecipitation (Co-IP) assay and transcriptome sequencing. Previous studies showed that compared with healthy tissues, the expression level of BAP31 protein was found to be significantly higher in various types of cancer tissues, implying that BAP31 may serve an important role in the pathogenesis of cancer. The present study found that BAP31 expression was upregulated in five ovarian cancer cell lines and ovarian cancer tissue, such that BAP31 knockdown [performed using two short hairpin (sh)RNA plasmids] decreased proliferation, invasion and migration. In addition, BAP31 knockdown was found to downregulate the expression of N-cadherin and upregulate the expression of E-cadherin on transcriptional level by controlling the nuclear aggregation of TWIST1, a transcriptional regulator of N-cadherin and E-cadherin. There was no interaction between BAP31 and E-cadherin or N-cadherin using Co-IP detection, while BAP31, E-cadherin and N-cadherin interacted with TWIST1 protein. E-cadherin and N-cadherin expression levels recovered when TWIST1 was overexpressed in the shBCAP31 cells. These results suggest that BAP31 can regulate the migration and invasion of ovarian cancer cells through the epithelial-mesenchymal transition pathway at the transcriptional level, which may be beneficial for the identification of potentially novel targets for ovarian cancer therapy.

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Epithelial-to-mesenchymal transition–related transcription factors are up-regulated in ependymomas and correlate with a poor prognosis

Cited by 26 publications

References 32 publications

Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology

Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology

Transcriptional co-expression regulatory network analysis for Snail and Slug identifiesIL1R1, an inflammatory cytokine receptor, to be preferentially expressed in ST-EPN-RELAand PF-EPN-A molecular subgroups of intracranial ependymomas

B‑cell receptor‑associated protein 31 promotes migration and invasion in ovarian cancer cells

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