scholarly journals Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5726
Author(s):  
Federico Bocci ◽  
Peijie Zhou ◽  
Qing Nie
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Signaling ◽  
Single Cell ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Intermediate Cell ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Cell Cell

Intermediate cell states (ICSs) during the epithelial–mesenchymal transition (EMT) are emerging as a driving force of cancer invasion and metastasis. ICSs typically exhibit hybrid epithelial/mesenchymal characteristics as well as cancer stem cell (CSC) traits including proliferation and drug resistance. Here, we analyze several single-cell RNA-seq (scRNA-seq) datasets to investigate the relation between several axes of cancer progression including EMT, CSC traits, and cell–cell signaling. To accomplish this task, we integrate computational methods for clustering and trajectory inference with analysis of EMT gene signatures, CSC markers, and cell–cell signaling pathways, and highlight conserved and specific processes across the datasets. Our analysis reveals that “standard” measures of pluripotency often used in developmental contexts do not necessarily correlate with EMT progression and expression of CSC-related markers. Conversely, an EMT circuit energy that quantifies the co-expression of epithelial and mesenchymal genes consistently increases along EMT trajectories across different cancer types and anatomical locations. Moreover, despite the high context specificity of signal transduction across different cell types, cells undergoing EMT always increased their potential to send and receive signals from other cells.

scholarly journals Cooperation of Cancer Stem Cell Properties and Epithelial-Mesenchymal Transition in the Establishment of Breast Cancer Metastasis

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Tetsu Hayashida ◽  
Hiromitsu Jinno ◽  
Yuko Kitagawa ◽  
Masaki Kitajima
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Breast Cancer Metastasis ◽  
Cell Junctions ◽  
Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) is a multistep process in which cells acquire molecular alterations such as loss of cell-cell junctions and restructuring of the cytoskeleton. There is an increasing understanding that this process may promote breast cancer progression through promotion of invasive and metastatic tumor growth. Recent observations imply that there may be a cross-talk between EMT and cancer stem cell properties, leading to enhanced tumorigenicity and the capacity to generate heterogeneous tumor cell populations. Here, we review the experimental and clinical evidence for the involvement of EMT in cancer stem cell theory, focusing on the common characteristics of this phenomenon.

scholarly journals Characterizing Intercellular Communication of Pan-Cancer Reveals SPP1+ Tumor-Associated Macrophage Expanded in Hypoxia and Promoting Cancer Malignancy Through Single-Cell RNA-Seq Data

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinfen Wei ◽  
Zixi Chen ◽  
Meiling Hu ◽  
Ziqing He ◽  
Dawei Jiang ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Single Cells ◽  
Matrix Remodeling ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Tumor Associated Macrophage ◽  
Cancer Types

Hypoxia is a characteristic of tumor microenvironment (TME) and is a major contributor to tumor progression. Yet, subtype identification of tumor-associated non-malignant cells at single-cell resolution and how they influence cancer progression under hypoxia TME remain largely unexplored. Here, we used RNA-seq data of 424,194 single cells from 108 patients to identify the subtypes of cancer cells, stromal cells, and immune cells; to evaluate their hypoxia score; and also to uncover potential interaction signals between these cells in vivo across six cancer types. We identified SPP1+ tumor-associated macrophage (TAM) subpopulation potentially enhanced epithelial–mesenchymal transition (EMT) by interaction with cancer cells through paracrine pattern. We prioritized SPP1 as a TAM-secreted factor to act on cancer cells and found a significant enhanced migration phenotype and invasion ability in A549 lung cancer cells induced by recombinant protein SPP1. Besides, prognostic analysis indicated that a higher expression of SPP1 was found to be related to worse clinical outcome in six cancer types. SPP1 expression was higher in hypoxia-high macrophages based on single-cell data, which was further validated by an in vitro experiment that SPP1 was upregulated in macrophages under hypoxia-cultured compared with normoxic conditions. Additionally, a differential analysis demonstrated that hypoxia potentially influences extracellular matrix remodeling, glycolysis, and interleukin-10 signal activation in various cancer types. Our work illuminates the clearer underlying mechanism in the intricate interaction between different cell subtypes within hypoxia TME and proposes the guidelines for the development of therapeutic targets specifically for patients with high proportion of SPP1+ TAMs in hypoxic lesions.

scholarly journals USP29 enhances chemotherapy-induced stemness in non-small cell lung cancer via stabilizing Snail1 in response to oxidative stress

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Yueguang Wu ◽  
Yingqiu Zhang ◽  
Duchuang Wang ◽  
Yang Zhang ◽  
Jinrui Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Transcriptional Activation ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
E3 Ligases ◽  
Tumor Dissemination

Abstract Chemotherapy remains an essential part of diverse treatment regimens against human malignancies. However, recent progressions have revealed a paradoxical role of chemotherapies to induce the cancer stem cell-like features that facilitate chemoresistance and tumor dissemination, with the underlying mechanisms underinvestigated. The zinc-finger transcription factor Snail1 is a central regulator during the epithelial-mesenchymal transition process and is closely implicated in cancer progression. Snail1 expression is strictly regulated at multiple layers, with its stability governed by post-translational ubiquitylation that is counterbalanced by the activities of diverse E3 ligases and deubiquitylases. Here we identify the deubiquitylase USP29 as a novel stabilizer of Snail1, which potently restricts its ubiquitylation in a catalytic activity-dependent manner. Bioinformatic analysis reveals a reverse correlation between USP29 expression and prognosis in lung adenocarcinoma patients. USP29 is unique among Snail1 deubiquitylases through exhibiting chemotherapy-induced upregulation. Mechanistically, oxidative stresses incurred by chemotherapy stimulate transcriptional activation of USP29. USP29 upregulation enhances the cancer stem cell-like characteristics in lung adenocarcinoma cells to promote tumorigenesis in athymic nude mice. Our findings uncover a novel mechanism by which chemotherapy induces cancer stemness and suggest USP29 as a potential therapeutic target to impede the development of chemoresistance and metastasis in lung adenocarcinoma.

scholarly journals Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells

Tumor Biology ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 101042832097943
Author(s):  
Natalia Ospina-Muñoz ◽  
Jean-Paul Vernot
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
First Generation ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Interleukin 8 ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Sphere Formation ◽  
Mcf 7

The interleukin-8 is an important regulator of the tumor microenvironment, promoting the epithelial–mesenchymal transition and the acquisition of stem-like cell properties in cancer cells. The tumorsphere-formation assay has been used for the identification of cancer stem cell. Interleukin-8 induces the formation of larger tumorspheres in Michigan Cancer Foundation-7 (MCF-7) cells, suggesting cancer stem cell enrichment. In this work, we aimed to study the phenotypic and functional characteristics of the cells present within the tumorspheres of MCF-7 cells previously treated with interleukin-8. MCF-7 cells treated for 5 days or not with this cytokine were further cultivated in ultralow attachment plates for another 5 days to allow tumorspheres formation. We showed that the enhanced sphere formation by MCF-7 cells was not a consequence of higher cell proliferation by interleukin-8 stimulation. Despite maintaining an epithelial–mesenchymal transition phenotype with the presence of epithelial and mesenchymal markers, basic stemness properties were impaired in tumorspheres and in those treated with interleukin-8, while others were increased. Self-renewal capacity was increased in interleukin-8-treated cells only in the first generation of tumorspheres but was not sustained in consecutive assays. Accordingly, self-renewal and reprogramming gene expression, differentiation capacity to adipocytes, and clonogenicity were also impaired. We showed also that tumorspheres were enriched in differentiated luminal cells (EpCAM+/CD49f−). Nevertheless, cells were more quiescent and maintain a partial epithelial–mesenchymal transition, consistent with their increased resistance to Paclitaxel and Doxorubicin. They also presented higher migration and interleukin-8-directed invasion. Therefore, the breast cancer cell line MCF-7, having a low stemness index, might partially acquire some stem-like cell attributes after interleukin-8 stimulation, increasing its aggressiveness.

scholarly journals Helicobacter pylori generates cells with cancer stem cell properties via epithelial–mesenchymal transition-like changes

Oncogene ◽  
2013 ◽  
Vol 33 (32) ◽  
pp. 4123-4131 ◽  
Author(s):  
E Bessède ◽  
C Staedel ◽  
L A Acuña Amador ◽  
P H Nguyen ◽  
L Chambonnier ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition
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