Contribution of cells undergoing epithelial–mesenchymal transition to the tumour microenvironment

2013 ◽  
Vol 78 ◽  
pp. 545-557 ◽  
Author(s):  
Rommel A. Mathias ◽  
Shashi K. Gopal ◽  
Richard J. Simpson
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Mesenchymal Transition

scholarly journals Recent Advances: The Imbalance of Immune Cells and Cytokines in the Pathogenesis of Hepatocellular Carcinoma

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 338
Author(s):  
Kumar Jayant ◽  
Nagy Habib ◽  
Kai W. Huang ◽  
Jane Warwick ◽  
Ramesh Arasaradnam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Liver Parenchyma ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Inflammatory State

Recent advancement in the immunological understanding of genesis of hepatocellular carcinoma (HCC) has implicated a decline in anti-tumour immunity on the background of chronic inflammatory state of liver parenchyma. The development of HCC involves a network of immunological activity in the tumour microenvironment involving continuous interaction between tumour and stromal cells. The reduction in anti-tumour immunity is secondary to changes in various immune cells and cytokines, and the tumour microenvironment plays a critical role in modulating the process of liver fibrosis, hepatocarcinogenesis, epithelial-mesenchymal transition (EMT), tumor invasion and metastasis. Thus, it is considered as one of primary factor behind the despicable tumour behavior and observed poor survival; along with increased risk of recurrence following treatment in HCC. The primary intent of the present review is to facilitate the understanding of the complex network of immunological interactions of various immune cells, cytokines and tumour cells associated with the development and progression of HCC.

scholarly journals Role of circadian rhythm disorders in EMT and tumor–immune interactions in endocrine-related cancers

2021 ◽  
Author(s):  
Eva Hadadi ◽  
Hervé Acloque
Keyword(s):  
Circadian Rhythm ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Tumour Microenvironment ◽  
Tissue Level ◽  
Mesenchymal Transition ◽  
Animal Physiology ◽  
Molecular Machinery ◽  
Epithelial Tumours ◽  
Cell Dissemination

The circadian rhythm is a major environmental regulator of plants and animal physiology. The alternation of days and nights is translated at the cell and tissue level thanks to a molecular machinery, called the circadian clock. This clock controls in particular numerous endocrine functions and its imbalances can have serious consequences on homeostasis. This is particularly true for the development of endocrine-related cancers, like breast, ovarian and prostate cancer. Circadian rhythm disorder (CRD) not only affects key hormone levels (including estrogen, melatonin, insulin, glucagon, cortisol) but also favors a pro-inflammatory and immunosuppressive phenotype in the tumour microenvironment. This particular aspect is conducive to epithelial-mesenchymal transition (EMT) of solid epithelial tumours and cancer cell dissemination. It also favors resistance to chemo- and immunotherapy. Here, we discuss the current knowledge on this crosstalk between CRD, EMT and the immune microenvironment in endocrine-related cancers and its consequences for the development of efficient therapies.

scholarly journals DNAJB6 governs a novel regulatory loop determining Wnt/β-catenin signalling activity

2012 ◽  
Vol 444 (3) ◽  
pp. 573-580 ◽  
Author(s):  
Mitchell E. Menezes ◽  
Aparna Mitra ◽  
Lalita A. Shevde ◽  
Rajeev S. Samant
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Negative Control ◽  
Signalling Pathway ◽  
Transition Analysis ◽  
Mesenchymal Transition ◽  
Tumour Metastasis ◽  
Dkk1 Expression ◽  
Exogenous Expression ◽  
Regulatory Loop

DKK1 (dickkopf 1 homologue) is a secreted inhibitor of the Wnt signalling pathway and a critical modulator of tumour promotion and the tumour microenvironment. However, mechanisms regulating DKK1 expression are understudied. DNAJB6 {DnaJ [HSP40 (heat-shock protein 40 kDa)] homologue, subfamily B, member 6} is an HSP40 family member whose expression is compromized during progression of breast cancer and melanoma. Inhibition of the Wnt/β-catenin signalling pathway by up-regulation of DKK1 is one of the key mechanisms by which DNAJB6 suppresses tumour metastasis and EMT (epithelial–mesenchymal transition). Analysis of the DKK1 promoter to define the cis-site responsible for its up-regulation by DNAJB6 revealed the presence of two binding sites for a transcriptional repressor, MSX1 (muscle segment homeobox 1). Our investigations showed that MSX1 binds the DKK1 promoter and inhibits DKK1 transcription. Interestingly, silencing DNAJB6 resulted in up-regulation of MSX1 concomitant with increased stabilization of β-catenin. ChIP (chromatin immunoprecipitation) studies revealed that β-catenin binds the MSX1 promoter and stabilization of β-catenin elevates MSX1 transcription, indicating that β-catenin works as a transcription co-activator for MSX1. Functionally, exogenous expression of MSX1 in DNAJB6-expressing cells promotes the mesenchymal phenotype by suppression of DKK1. Thus we have identified a novel regulatory mechanism of DNAJB6-mediated DKK1 transcriptional up-regulation that can influence EMT. DKK1 is a feedback regulator of β-catenin levels and thus our studies also define an additional negative control of this β-catenin/DKK1 feedback loop by MSX1, which may potentially contribute to excessive stabilization of β-catenin.

scholarly journals Tiny miRNAs Play a Big Role in the Treatment of Breast Cancer Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 337
Author(s):  
Andrea York Tiang Teo ◽  
Xiaoqiang Xiang ◽  
Minh TN Le ◽  
Andrea Li-Ann Wong ◽  
Qi Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Breast Cancer Metastasis ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Recent Developments ◽  
Underlying Mechanisms

Distant organ metastases accounts for the majority of breast cancer deaths. Given the prevalence of breast cancer in women, it is imperative to understand the underlying mechanisms of its metastatic progression and identify potential targets for therapy. Since their discovery in 1993, microRNAs (miRNAs) have emerged as important regulators of tumour progression and metastasis in various cancers, playing either oncogenic or tumour suppressor roles. In the following review, we discuss the roles of miRNAs that potentiate four key areas of breast cancer metastasis—angiogenesis, epithelial-mesenchymal transition, the Warburg effect and the tumour microenvironment. We then evaluate the recent developments in miRNA-based therapies in breast cancer, which have shown substantial promise in controlling tumour progression and metastasis. Yet, certain challenges must be overcome before these strategies can be implemented in clinical trials.

scholarly journals Expression of FSCN1 and FOXM1 are associated with poor prognosis of adrenocortical carcinoma patients

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiayu Liang ◽  
Zhihong Liu ◽  
Xin Wei ◽  
Liang Zhou ◽  
Yongquan Tang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Adrenocortical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumour Microenvironment ◽  
The Cancer Genome Atlas ◽  
Adrenocortical Adenoma ◽  
Mesenchymal Transition ◽  
Over Expression

Abstract Background Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs. Methods Clinical and specimen data from 130 adrenocortical carcinoma (ACC) patients was acquired from the Cancer Genome Atlas (TCGA) database (n = 79) and a West China Hospital (WCH) cohort (n = 51). In the WCH cohort, archived formalin-fixed paraffin embedded (FFPE) samples were collected for immunohistochemical analysis. The correlation between the EMT genes and the tumour microenvironment status was estimated based on the Tumour Immune Estimation Resource (TIMER) algorithm. Kaplan-Meier analysis, followed by univariate and multivariate regression analyses, were performed to identify the prognostic association of FSCN1 and FOXM1. Results FSCN1 and FOXM1 were over-expressed in ACC tissue when compared with adrenocortical adenoma and normal adrenal tissue. Over-expression of FSCN1 or FOXM1 was associated with the tumour microenvironment and immune signatures in ACCs. Patients with higher expression of FSCN1 or FOXM1 were more likely to have worse prognoses. The prognostic effects were further verified in both early (stage I/II) and advanced (stage III/IV) ACCs. Furthermore, FSCN1 and FOXM1 appeared as independent prognostic factors in ACC. Conclusions These results show that FSCN1 and FOXM1 are independent prognostic factors in ACCs and over-expression of FSCN1 or FOXM1 indicates a worse prognosis.

scholarly journals Role of extracellular vesicles in tumour microenvironment

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Shi-Cong Tao ◽  
Shang-Chun Guo
Keyword(s):  
Extracellular Vesicles ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Progression ◽  
Malignant Tumour ◽  
Tumour Microenvironment ◽  
Future Research ◽  
Malignant Cells ◽  
Malignant Tumours ◽  
Mesenchymal Transition

Abstract In recent years, it has been demonstrated that extracellular vesicles (EVs) can be released by almost all cell types, and detected in most body fluids. In the tumour microenvironment (TME), EVs serve as a transport medium for lipids, proteins, and nucleic acids. EVs participate in various steps involved in the development and progression of malignant tumours by initiating or suppressing various signalling pathways in recipient cells. Although tumour-derived EVs (T-EVs) are known for orchestrating tumour progression via systemic pathways, EVs from non-malignant cells (nmEVs) also contribute substantially to malignant tumour development. Tumour cells and non-malignant cells typically communicate with each other, both determining the progress of the disease. In this review, we summarise the features of both T-EVs and nmEVs, tumour progression, metastasis, and EV-mediated chemoresistance in the TME. The physiological and pathological effects involved include but are not limited to angiogenesis, epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) remodelling, and immune escape. We discuss potential future directions of the clinical application of EVs, including diagnosis (as non-invasive biomarkers via liquid biopsy) and therapeutic treatment. This may include disrupting EV biogenesis and function, thus utilising the features of EVs to repurpose them as a therapeutic tool in immunotherapy and drug delivery systems. We also discuss the overall findings of current studies, identify some outstanding issues requiring resolution, and propose some potential directions for future research.

scholarly journals A mathematical multi-organ model for bidirectional epithelial–mesenchymal transitions in the metastatic spread of cancer

2020 ◽  
Vol 85 (5) ◽  
pp. 724-761 ◽  
Author(s):  
Linnea C Franssen ◽  
Mark A J Chaplain
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
The Body ◽  
Metastatic Spread ◽  
Mathematical Framework ◽  
Mesenchymal Transition ◽  
Epithelial Phenotype ◽  
Organ Model ◽  
Cell Dormancy

Abstract Cancer invasion and metastatic spread to secondary sites in the body are facilitated by a complex interplay between cancer cells of different phenotypes and their microenvironment. A trade-off between the cancer cells’ ability to invade the tissue and to metastasize, and their ability to proliferate has been observed. This gives rise to the classification of cancer cells into those of mesenchymal and epithelial phenotype, respectively. Additionally, mixed phenotypic states between these two extremes exist. Cancer cells can transit between these states via epithelial–mesenchymal transition (EMT) and the reverse process, mesenchymal–epithelial transition (MET). These processes are crucial for both the local tissue invasion and the metastatic spread of cancer cells. To shed light on the role of these phenotypic states and the transitions between them in the invasive and metastatic process, we extend our recently published multi-grid, hybrid, individual-based mathematical metastasis framework (Franssen et al. 2019, A mathematical framework for modelling the metastatic spread of cancer. Bull. Math. Biol., 81, 1965). In addition to cancer cells of epithelial and of mesenchymal phenotype, we now also include those of an intermediate partial-EMT phenotype. Furthermore, we allow for the switching between these phenotypic states via EMT and MET at the biologically appropriate steps of the invasion-metastasis cascade. We also account for the likelihood of spread of cancer cells to the various secondary sites and differentiate between the tissues of the organs involved in our simulations. Finally, we consider the maladaptation of metastasized cancer cells to the new tumour microenvironment at secondary sites as well as the immune response at these sites by accounting for cancer cell dormancy and death. This way, we create a first mathematical multi-organ model that explicitly accounts for EMT-processes occurring at the level of individual cancer cells in the context of the invasion-metastasis cascade.

scholarly journals Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 692 ◽  
Author(s):  
Geoffroy Walbrecq ◽  
Odile Lecha ◽  
Anthoula Gaigneaux ◽  
Miriam R. Fougeras ◽  
Demetra Philippidou ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Tumour Microenvironment ◽  
Extracellular Vesicle ◽  
Growth Conditions ◽  
Melanoma Cells ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition

Reduced levels of intratumoural oxygen are associated with hypoxia-induced pro-oncogenic events such as invasion, metabolic reprogramming, epithelial–mesenchymal transition, metastasis and resistance to therapy, all favouring cancer progression. Small extracellular vesicles (EV) shuttle various cargos (proteins, miRNAs, DNA and others). Tumour-derived EVs can be taken up by neighbouring or distant cells in the tumour microenvironment, thus facilitating intercellular communication. The quantity of extracellular vesicle secretion and their composition can vary with changing microenvironmental conditions and disease states. Here, we investigated in melanoma cells the influence of hypoxia on the content and number of secreted EVs. Whole miRNome and proteome profiling revealed distinct expression patterns in normoxic or hypoxic growth conditions. Apart from the well-known miR-210, we identified miR-1290 as a novel hypoxia-associated microRNA, which was highly abundant in hypoxic EVs. On the other hand, miR-23a-5p and -23b-5p were consistently downregulated in hypoxic conditions, while the protein levels of the miR-23a/b-5p-predicted target IPO11 were concomitantly upregulated. Furthermore, hypoxic melanoma EVs exhibit a signature consisting of six proteins (AKR7A2, DDX39B, EIF3C, FARSA, PRMT5, VARS), which were significantly associated with a poor prognosis for melanoma patients, indicating that proteins and/or miRNAs secreted by cancer cells may be exploited as biomarkers.

scholarly journals The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2788
Author(s):  
Robert Tempest ◽  
Sonia Guarnerio ◽  
Rawan Maani ◽  
Jamie Cooper ◽  
Nicholas Peake
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Transglutaminase 2 ◽  
Biomechanical Properties ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Tissue Remodelling ◽  
Direct Role ◽  
Mesenchymal Transition ◽  
Cellular Processes

Transglutaminase-2 (TG2) is the most highly and ubiquitously expressed member of the transglutaminase enzyme family and is primarily involved in protein cross-linking. TG2 has been implicated in the development and progression of numerous cancers, with a direct role in multiple cellular processes and pathways linked to apoptosis, chemoresistance, epithelial-mesenchymal transition, and stem cell phenotype. The tumour microenvironment (TME) is critical in the formation, progression, and eventual metastasis of cancer, and increasing evidence points to a role for TG2 in matrix remodelling, modulation of biomechanical properties, cell adhesion, motility, and invasion. There is growing interest in targeting the TME therapeutically in response to advances in the understanding of its critical role in disease progression, and a number of approaches targeting biophysical properties and biomechanical signalling are beginning to show clinical promise. In this review we aim to highlight the wide array of processes in which TG2 influences the TME, focussing on its potential role in the dynamic tissue remodelling and biomechanical events increasingly linked to invasive and aggressive behaviour. Drug development efforts have yielded a range of TG2 inhibitors, and ongoing clinical trials may inform strategies for targeting the biomolecular and biomechanical function of TG2 in the TME.

Sign in / Sign up

Export Citation Format

Share Document