The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

Markiewicz, Aleksandra; Żaczek, Anna

doi:10.1159/000477812

Cited by 16 publications

(19 citation statements)

References 162 publications

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“…Polioudaki and colleagues described that CTCs undergoing EMT acquired mesenchymal morphology, which was associated with full or partial CK19 replacement by Vimentin [35]. The EMT status of CTCs has been a matter of controversy, with some studies pointing to an association between tumor cells with partial EMT state and a worse outcome, when compared with cells that have undergone complete EMT [54][55][56][57]. In addition, it has been postulated that EMT is not enough for metastasis in a number of cancer types [58][59][60], and a recent publication by Padmanaban and colleagues described that E-Cadherin was required for metastasis [61], reinforcing the role of epithelial markers in this process.…”

Section: Discussionmentioning

confidence: 99%

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Pereira-Veiga¹,

Martínez‐Fernández

Abuín³

et al. 2019

Cancers

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The study of circulating tumor cells (CTCs) has a huge clinical interest in advance and metastatic breast cancer patients. However, many approaches are biased by the use of epithelial markers, which underestimate non-epithelial CTCs phenotypes. CTCs enumeration provides valuable prognostic information; however, molecular characterization could be the best option to monitor patients throughout the disease since it may provide more relevant clinical information to the physicians. In this work, we aimed at enumerating and performing a molecular characterization of CTCs from a cohort of 20 patients with metastatic breast cancer (MBC), monitoring the disease at different time points of the therapy, and at progression when it occurred. To this end, we used a CTC negative enrichment protocol that allowed us to recover a higher variety of CTCs phenotypes. With this strategy, we were able to obtain gene expression data from CTCs from all the patients. In addition, we found that high expression levels of PALB2 and MYC were associated with a worse outcome. Interestingly, we identified that CTCs with an EpCAMhighVIMlowALDH1A1high signature showed both shorter overall survival (OS) and progression-free survival (PFS), suggesting that CTCs with epithelial-stem features had the most aggressive phenotype.

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Section: Discussionmentioning

confidence: 99%

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Pereira-Veiga¹,

Martínez‐Fernández

Abuín³

et al. 2019

Cancers

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“…They require the formation of clusters together with stromal cells (e.g., fibroblasts, endothelial, tumorinfiltrated myeloid cells, or pericytes) to increase the viability of tumor progression, as shown in Figure 2. Pericytes promote the formation of CTC groups termed as circulating tumor microemboli, which are formed by 2-50 CTC with improved metastatic potential and tumor progression (15,93).…”

Section: Migrating Csc and Metastasismentioning

confidence: 99%

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

et al. 2020

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Colorectal carcinoma (CRC) is a leading cause of cancer mortality. Tumorigenesis is a dynamic process wherein cancer stem cells (CSCs) and their microenvironment promote initiation, progression, and metastasis. Metastatic colonization is an inefficient process that is very complex and is poorly understood; however, in most cases, metastatic disease is not curable, and resistance mechanisms tend to develop against conventional treatments. An understanding of the underlying mechanisms and factors that contribute to the development of metastasis in CRC can aid in the search for specific therapeutic targets for improving standard treatments. In this review, we summarize current knowledge regarding tumor biology and the use of stroma cells as prognostic factors and inflammatory inducers associated with the use of tumor microenvironments as a promoter of cancer metastasis. Moreover, we look into the importance of CSC, pericytes, and circulating tumor cells as mechanisms that lead to liver metastasis, and we also focus on the cellular and molecular pathways that modulate and regulate epithelial-mesenchymal transition. Finally, we discuss a novel therapeutic target that can potentially eliminate CSCs as a CRC treatment.

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“…Epithelialmesenchymal transitions (EMTs), providing tumor cells with enhanced invasive, survival, stemness, and niching properties, have rapidly been recognized key processes in the biology of CTCs liberated from epithelial tumors [4][5][6][7]. Accordingly, the expression of EMT actors (e.g., vimentin, Twist, Snail, or ZEB1) has been detected in CTCs in animal models and extensively reported in subpopulations of CTCs isolated from cancer patients [4,[7][8][9]. It is thus today considered that EMT-shifted CTCs encompass subpopulations of metastasis initiating cells.…”

Section: Introductionmentioning

confidence: 99%

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

et al. 2020

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Epithelial-mesenchymal transitions (EMTs) are high-profile in the field of circulating tumor cells (CTCs). EMT-shifted CTCs are considered to encompass pre-metastatic subpopulations though underlying molecular mechanisms remain elusive. Our previous work identified tissue factor (TF) as an EMT-induced gene providing tumor cells with coagulant properties and supporting metastatic colonization by CTCs. We here report that vimentin, the type III intermediate filament considered a canonical EMT marker, contributes to TF regulation and positively supports coagulant properties and early metastasis. Different evidence further pointed to a new post-transcriptional regulatory mechanism of TF mRNA by vimentin: (1) vimentin silencing accelerated TF mRNA decay after actinomycin D treatment, reflecting TF mRNA stabilization, (2) RNA immunoprecipitation revealed enriched levels of TF mRNA in vimentin immunoprecipitate, (3) TF 3′-UTR-luciferase reporter vector assays implicated the 3′-UTR of TF mRNA in vimentin-dependent TF regulation, and (4) using different TF 3′UTR-luciferase reporter vectors mutated for potential miR binding sites and specific Target Site Blockers identified a key miR binding site in vimentin-dependent TF mRNA regulation. All together, these data support a novel mechanism by which vimentin interferes with a miR-dependent negative regulation of TF mRNA, thereby promoting coagulant activity and early metastasis of vimentin-expressing CTCs.

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The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

Cited by 16 publications

References 162 publications

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

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