EMT in Metastasis: Finding the Right Balance

Lo, Hin Ching; Zhang, Xiang H.-F.

doi:10.1016/j.devcel.2018.05.033

Cited by 39 publications

(35 citation statements)

References 10 publications

(11 reference statements)

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“…Transitions between epithelial and mesenchymal phenotypes (the epithelial to mesenchymal transition [EMT] and its reverse, the mesenchymal to epithelial transition [MET]), are hallmarks of cancer metastasis . The connection among EMT, MET and stemness indicates that CSC come in two distinct states: “epithelial‐like” and “mesenchymal‐like.” Recent studies have attempted to resolve this contradiction by suggesting that instead of the cells in pure epithelial (E) or pure mesenchymal (M) states, cells in hybrid E/M or partial EMT state (which express epithelial and mesenchymal markers concurrently) are most likely to gain stemness . In fact, many CTC that survive in blood exhibit hybrid E/M phenotypes, become resistant to drugs and exit the bloodstream more efficiently .…”

Section: Introductionmentioning

confidence: 99%

Cancer stem‐like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion

Quan

Wang

et al. 2020

Cancer Science

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Collective invasion of cancer cells is the key process of circulating tumor cell (CTC) cluster formation, and greatly contributes to metastasis. Cancer stem-like cells (CSC) have a distinct advantage of motility for metastatic dissemination. To verify the role of CSC in the collective invasion, we performed 3D assays to investigate the collective invasion from cancer cell spheroids. The results demonstrated that CSC can significantly promote both collective and single-cell invasion. Further study showed that CSC prefer to move outside and lead the collective invasion. More interestingly, approximately 60% of the leader CSC in collective invasion co-expressed both epithelial and mesenchymal genes, while only 4% co-expressed in single invasive CSC, indicating that CSC with hybrid epithelial/mesenchymal phenotype play a key role in cancer cell collective invasion. K E Y W O R D Scancer stem-like cells, collective invasion, hybrid epithelial/mesenchymal, leader, single invasion

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Section: Introductionmentioning

confidence: 99%

Cancer stem‐like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion

Quan

Wang

et al. 2020

Cancer Science

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“…Depending on the characteristics of the primary tumor, the stroma, and the intrinsic ability of metastatic tumor cells to adapt to a new location, malignant cells use distinct mechanisms for proliferation, survival, and dissemination. These cells often reactivate the expression of genes employed during embryogenesis [17,18]. In order to leave the primary tumor and disseminate to distant organs, metastatic cells lose the ability to adhere to adjacent cells, enhancing their migratory and invasive capacity.…”

Section: Discussionmentioning

confidence: 99%

“…In order to leave the primary tumor and disseminate to distant organs, metastatic cells lose the ability to adhere to adjacent cells, enhancing their migratory and invasive capacity. This mechanism is accompanied by several modifications in the expression of genes, such as loss of epithelial receptor expression and increased expression of mesenchymal markers, a phenomenon also known as epithelial-mesenchymal transition [18,19].…”

Section: Discussionmentioning

confidence: 99%

Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data

et al. 2019

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Schwann cells were identified in the tumor surrounding area prior to initiate the invasion process underlying connective tissue. These cells promote cancer invasion through direct contact, while paracrine signaling and matrix remodeling are not sufficient to proceed. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of Schwann cells associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. Gene set over-representation analyses was performed on core DEGs to identify significantly functional and pathway enrichment analysis between Schwann cells and, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). DEGs were further integrated with genomescale human biomolecular networks. miRNAs were proposed by the reconstruction of a transcriptional and post-transcriptional regulatory network. Moreover, microarraybased transcriptome profiling was performed, and the prognostic power of selected dedifferentiated Schwann cell biomolecules was predicted. We observed that pathways associated with Schwann cells dedifferentiation was overexpressed in lung cancer samples. However, genes associated with Schwann cells migration inhibition system were downregulated. Besides, miRNA targeting those pathways were also deregulated. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in perineural invasion of lung cancer.

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“…Focusing on the diverse regulated molecules, multiple drugs have shown their potential as EMT inhibitors by targeting the tumor microenvironment, corresponding extracellular receptors, intracellular kinases and EMT inducing transcription factors [15]. As its well-described clinical signature of EMT in cancer development, therapeutic strategies and targeted drugs towards EMT have been involved in cancer treatment [16][17][18].NF-κB is an important transcription factor involved in multiple biologic processes as immune response, stress response, apoptosis, cell proliferation and cell metastasis [18]. The abnormal activation of NF-κB has been regarded as a hallmark of cancer, which promotes both tumorigenesis and tumor development [19][20][21].…”

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confidence: 99%

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confidence: 99%

(20S)G-Rh2 Inhibits NF-κB Regulated Epithelial-Mesenchymal Transition by Targeting Annexin A2

Wang

et al. 2020

Biomolecules

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(1) Background: Epithelial-mesenchymal transition (EMT) is an essential step for cancer metastasis; targeting EMT is an important path for cancer treatment and drug development. NF-κB, an important transcription factor, has been shown to be responsible for cancer metastasis by enhancing the EMT process. Our previous studies showed that (20S)Ginsenoside Rh2 (G-Rh2) inhibits NF-κB activity by targeting Anxa2, but it is still not known whether this targeted inhibition of NF-κB can inhibit the EMT process. (2) Methods: In vivo (20S)G-Rh2-Anxa2 interaction was assessed by cellular thermal shift assay. Protein interaction was determined by immuno-precipitation analysis. NF-κB activity was determined by dual luciferase reporter assay. Gene expression was determined by RT-PCR and immuno-blot. EMT was evaluated by wound healing and Transwell assay and EMT regulating gene expression. (3) Results: Anxa2 interacted with the NF-κB p50 subunit, promoted NF-κB activation, then accelerated mesenchymal-like gene expression and enhanced cell motility; all these cellular processes were inhibited by (20S)G-Rh2. In contrast, these (20S)G-Rh2 effect were completely eliminated by overexpression of Anxa2-K301A, an (20S)G-Rh2-binding-deficient mutant of Anxa2. (4) Conclusion: (20S)G-Rh2 inhibited NF-κB activation and related EMT by targeting Anxa2 in MDA-MB-231 cells.

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EMT in Metastasis: Finding the Right Balance

Cited by 39 publications

References 10 publications

Cancer stem‐like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion

Cancer stem‐like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion

Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data

(20S)G-Rh2 Inhibits NF-κB Regulated Epithelial-Mesenchymal Transition by Targeting Annexin A2

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