ORCID Profile
0000-0002-5918-4276
Current Organisation
Brown University
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Publisher: MDPI AG
Date: 18-09-2018
DOI: 10.3390/NCRNA4030023
Abstract: We are delighted to share with you our sixth Journal Club and highlight some of the most interesting papers published recently [...]
Publisher: Springer Science and Business Media LLC
Date: 16-04-2020
DOI: 10.1038/S41580-020-0237-9
Abstract: Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a erse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining ersity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
Publisher: Cold Spring Harbor Laboratory
Date: 27-05-2019
DOI: 10.1101/651620
Abstract: The epithelial-mesenchymal transition (EMT) often plays a critical role in cancer metastasis and chemoresistance, and decoding its dynamics is crucial to design effective therapeutics. EMT is regulated at multiple levels transcriptional, translational, protein stability, and epigenetics the mechanisms by which epigenetic regulation can alter the dynamics of EMT remain elusive. Here, to identify the possible effects of epigenetic regulation in EMT, we incorporate a feedback term in our previously proposed model of EMT regulation of the miR 200/ZEB/miR 34/SNAIL circuit. This epigenetic feedback that stabilizes long-term transcriptional activity can alter the relative stability and distribution of states in a given cell population, particularly when incorporated in the inhibitory effect on miR 200 from ZEB. This feedback can stabilize the mesenchymal state, thus making transitions out of that state difficult. Conversely, epigenetic regulation of the self activation of ZEB has only minor effects. Our model predicts that this effect could be seen in experiments, when epithelial cells are treated with an external EMT inducing signal for a sufficiently long period of time and then allowed to recover. Our preliminary experimental data indeed shows that a prolonged TGF beta exposure gives rise to increasing difficult reversion back to the epithelial state. Thus, this integrated theoretical experimental approach yields insights into how an epigenetic feedback may alter the dynamics of EMT.
Publisher: Proceedings of the National Academy of Sciences
Date: 03-05-2021
Abstract: The epithelial-to-mesenchymal transition (EMT) is a critical cell biological process that occurs during normal embryonic development and cancer progression. Our study combines single-cell RNA-sequencing analysis and mathematical modeling to identify critical regulators of EMT. Detailed analyses of TGF-β1–induced EMT by single-cell RNA-sequencing data revealed simultaneous activation of EMT signaling pathways. We created mathematical approaches to identify the master regulatory pathway of EMT and key downstream mediators of this process. This study sheds light on the signaling architecture that governs EMT and informs ongoing efforts to delineate drivers of cancer initiation, progression, and metastasis.
Publisher: Cold Spring Harbor Laboratory
Date: 02-07-2021
DOI: 10.1101/2021.07.01.449976
Abstract: Cancer cells acquire stem cell and mesenchymal properties during epithelial-to-mesenchymal transition (EMT), facilitating metastasis and chemoresistance [1-6]. In this study, we find that mammary epithelial cells quickly develop mesenchymal phenotype in response to EMT-inducing signals however, acquiring stemness takes several days and always requires a preceding mesenchymal program. In addition, we observe that carcinoma cells, over a period of time, switch their cell ision from symmetrical differentiated type to symmetrical self-renewal type. Importantly, epithelial cells can gain mesenchymal properties without undergoing cell ision, but cell disivion is vital for these cells to gain stem cell properties during EMT. The EMT-induced stemness signature (SC-sig) is capable of predicting progression-free and overall-survival of breast cancer patients but not the EMT-induced mesenchymal signature (M-sig). Collectively, our findings demonstrate that the use of mesenchymal markers alone is insufficient to identify tumors with metastatic and chemoresistance potential and emphasize that the markers of EMT-induced stem cell program are central for clinical prediction. Most importantly, our data, for the first time, demonstrate that acquisition of stem cell properties during EMT depends on cell ision but not the mesenchymal program.
Publisher: MDPI AG
Date: 17-06-2015
DOI: 10.3390/NCRNA1010087
Abstract: The number of papers dealing with new modus operandi or new biological functions of non-coding RNAs published in recent years has indeed exploded. A simple search for ‘non-coding RNA’ in Pubmed on 10 June 2015 yielded 128,649 articles, half of which were published in the last 10 years [1]. Every researcher in this field knows that he has something to learn and can discover new ideas, new concepts or new tools from studies made in models others than the ones used in its lab. The Scientific board of Non-Coding RNA publishes here its first Journal Club and highlights, in about hundred words, a selection of the most interesting papers published recently. We hope we will tease your curiosity and encourage you to read full papers outside of your research area that you may not have read otherwise. [...]
Publisher: IOP Publishing
Date: 06-09-2019
Publisher: Springer Science and Business Media LLC
Date: 06-2010
DOI: 10.1007/S10911-010-9175-Z
Abstract: We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44(high)CD24(low). Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.
Publisher: Cold Spring Harbor Laboratory
Date: 24-06-2013
Abstract: The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2 , a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC , miR–17–5p, and miR–20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.
Publisher: Springer Science and Business Media LLC
Date: 10-12-2021
DOI: 10.1038/S41416-020-01178-9
Abstract: The epithelial-mesenchymal transition (EMT) enables dissociation of tumour cells from the primary tumour mass, invasion through the extracellular matrix, intravasation into blood vessels and colonisation of distant organs. Cells that revert to the epithelial state via the mesenchymal-epithelial transition cause metastases, the primary cause of death in cancer patients. EMT also empowers cancer cells with stem-cell properties and induces resistance to chemotherapeutic drugs. Understanding the driving factors of EMT is critical for the development of effective therapeutic interventions. This manuscript describes the generation of a database containing EMT gene signatures derived from cell lines, patient-derived xenografts and patient studies across cancer types and multiomics data and the creation of a web-based portal to provide a comprehensive analysis resource. EMTome incorporates (i) EMT gene signatures (ii) EMT-related genes with multiomics features across different cancer types (iii) interactomes of EMT-related genes (miRNAs, transcription factors, and proteins) (iv) immune profiles identified from The Cancer Genome Atlas (TCGA) cohorts by exploring transcriptomics, epigenomics, and proteomics, and drug sensitivity and (iv) clinical outcomes of cancer cohorts linked to EMT gene signatures. The web-based EMTome portal is a resource for primary and metastatic tumour research publicly available at www.emtome.org .
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 28-05-2021
DOI: 10.1038/S41523-021-00269-X
Abstract: Breast cancer is the most commonly diagnosed cancer in the USA. Although advances in treatment over the past several decades have significantly improved the outlook for this disease, most women who are diagnosed with estrogen receptor positive disease remain at risk of metastatic relapse for the remainder of their life. The cellular source of late relapse in these patients is thought to be disseminated tumor cells that reactivate after a long period of dormancy. The biology of these dormant cells and their natural history over a patient’s lifetime is largely unclear. We posit that research on tumor dormancy has been significantly limited by the lack of clinically relevant models. This review will discuss existing dormancy models, gaps in biological understanding, and propose criteria for future models to enhance their clinical relevance.
Location: United States of America
Location: No location found
Location: United States of America
No related grants have been discovered for Sendurai Mani.