MicroRNAs Provide Feedback Regulation of Epithelial-Mesenchymal Transition Induced by Growth Factors

2015 ◽  
Vol 231 (1) ◽  
pp. 120-129 ◽  
Author(s):  
Zailong Qin ◽  
Wei He ◽  
Jingqun Tang ◽  
Qiurong Ye ◽  
Wei Dang ◽  
...  
Keyword(s):  
Growth Factors ◽  
Epithelial Mesenchymal Transition ◽  
Feedback Regulation ◽  
Mesenchymal Transition

scholarly journals A possible role for epigenetic feedback regulation in the dynamics of the epithelial–mesenchymal transition (EMT)

2019 ◽  
Vol 16 (6) ◽  
pp. 066004 ◽  
Author(s):  
Wen Jia ◽  
Abhijeet Deshmukh ◽  
Sendurai A Mani ◽  
Mohit Kumar Jolly ◽  
Herbert Levine
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Feedback Regulation ◽  
Mesenchymal Transition

Growth Factors in Induction of Epithelial-Mesenchymal Transition and Metastasis

2011 ◽  
Vol 193 (1-2) ◽  
pp. 85-97 ◽  
Author(s):  
Nur Akmarina B.M. Said ◽  
Elizabeth D. Williams
Keyword(s):  
Growth Factors ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-β-Induced Epithelial-Mesenchymal Transition

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ting Gui ◽  
Yujing Sun ◽  
Aiko Shimokado ◽  
Yasuteru Muragaki
Keyword(s):  
Growth Factors ◽  
Protein Kinase ◽  
Epithelial Mesenchymal Transition ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Important Process ◽  
Mesenchymal Transition ◽  
Mitogen Activated Protein ◽  
And Function ◽  
External Signals

The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret external signals and respond appropriately, especially during the epithelial-mesenchymal transition (EMT). EMT is an important process during embryonic development, fibrosis, and tumor progression in which epithelial cells acquire mesenchymal, fibroblast-like properties and show reduced intercellular adhesion and increased motility. TGF-β signaling is the first pathway to be described as an inducer of EMT, and its relationship with the Smad family is already well characterized. Studies of four members of the MAPK family in different biological systems have shown that the MAPK and TGF-β signaling pathways interact with each other and have a synergistic effect on the secretion of additional growth factors and cytokines that in turn promote EMT. In this paper, we present background on the regulation and function of MAPKs and their cascades, highlight the mechanisms of MAPK crosstalk with TGF-β signaling, and discuss the roles of MAPKs in EMT.

scholarly journals Co-Activation of TGFβ and Wnt Signalling Pathways Abrogates EMT in Ovarian Cancer Cells

2017 ◽  
Vol 41 (4) ◽  
pp. 1336-1345 ◽  
Author(s):  
Tulika Mitra ◽  
Sib Sankar Roy
Keyword(s):  
Ovarian Cancer ◽  
Growth Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signalling ◽  
Luciferase Assay ◽  
Signalling Pathways ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Co Activation

Background/Aims: The aggressive property of ovarian cancer (OC) in terms of epithelial-mesenchymal transition (EMT), proliferation and metastasis are of major concern. Different growth factors including TGFβ are associated with regulating these molecular events but the underlying mechanisms remain unclear. The aim of this report is to decipher the regulation of EMT by co-activation of TGFβ and Wnt signalling cascades in gaining malignancy. Methods: The expression of the different components of signalling events were analyzed by QPCR, Western blot, Immunofluorescence microscopy and flow cytometry. β-catenin promoter activity was checked by luciferase assay. Results: We observed reduced EMT in ovarian cancer cells upon co-activation with TGFβ1 and LiCl as shown by the expressions of epithelial/mesenchymal markers and the EMT promoting factor, Snail1, accompanied by decrease in the invasion and migration of the cells compared to individual pathway activation. A detailed study of the mechanism suggested reduction in the β-catenin and p-GSK3b (Ser 9) levels to be the driving cause of this phenomenon, which was reversed upon co-activation with higher concentrations of LiCl. Conclusions: Therefore, tumourigenesis might be affected by the concentration of ligand/ growth factors for the respective signalling pathways activated in the tumour microenvironment and interaction between them might alter tumourigenesis.

scholarly journals Roles for growth factors and mutations in metastatic dissemination

2021 ◽  
Author(s):  
Nishanth Belugali Nataraj ◽  
Ilaria Marrocco ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Blood Vessels ◽  
Epithelial Mesenchymal Transition ◽  
Driver Mutations ◽  
Sequencing Data ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Step Process ◽  
Metastatic Cascade ◽  
Epigenetic Processes

Cancer is initiated largely by specific cohorts of genetic aberrations, which are generated by mutagens and often mimic active growth factor receptors, or downstream effectors. Once initiated cells outgrow and attract blood vessels, a multi-step process, called metastasis, disseminates cancer cells primarily through vascular routes. The major steps of the metastatic cascade comprise intravasation into blood vessels, circulation as single or collectives of cells, and eventual colonization of distant organs. Herein, we consider metastasis as a multi-step process that seized principles and molecular players employed by physiological processes, such as tissue regeneration and migration of neural crest progenitors. Our discussion contrasts the irreversible nature of mutagenesis, which establishes primary tumors, and the reversible epigenetic processes (e.g. epithelial–mesenchymal transition) underlying the establishment of micro-metastases and secondary tumors. Interestingly, analyses of sequencing data from untreated metastases inferred depletion of putative driver mutations among metastases, in line with the pivotal role played by growth factors and epigenetic processes in metastasis. Conceivably, driver mutations may not confer the same advantage in the microenvironment of the primary tumor and of the colonization site, hence phenotypic plasticity rather than rigid cellular states hardwired by mutations becomes advantageous during metastasis. We review the latest reported examples of growth factors harnessed by the metastatic cascade, with the goal of identifying opportunities for anti-metastasis interventions. In summary, because the overwhelming majority of cancer-associated deaths are caused by metastatic disease, understanding the complexity of metastasis, especially the roles played by growth factors, is vital for preventing, diagnosing and treating metastasis.

scholarly journals Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis

2021 ◽  
Vol 67 (6) ◽  
pp. 453-464
Author(s):  
T.A. Gureeva ◽  
O.S. Timoshenko ◽  
E.V. Kugaevskaya ◽  
N.I. Solovyova
Keyword(s):  
Signal Transduction ◽  
Growth Factors ◽  
Tumor Progression ◽  
Tyrosine Kinases ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Signal Transduction Pathways ◽  
Ecm Remodeling ◽  
Mesenchymal Transition ◽  
Cysteine Cathepsins

Cysteine cathepsins (Cts) also known as thiol proteinases belong to the superfamily of cysteine proteinases (EC 3.4.22). Cts are known as lysosomal proteases responsible for the intracellular proteins degradation. All Cts are synthesized as zymogens, activation of which occurs autocatalytically. Their activity is regulated by endogenous inhibitors. Cts can be secreted into the extracellular environment, which is of particular importance in tumor progression. Extracellular Cts not only hydrolyze extracellular matrix (ECM) proteins, but also contribute to ECM remodeling, processing and/or release of cell adhesion molecules, growth factors, cytokines and chemokines. In cancer, the expression and activity of Cts sharply increase both in cell lysosomes and in the intercellular space, which correlates with neoplastic transformation, invasion, metastasis and leads to further tumor progression. It has been shown that Cts expression depends on the cells type, therefore, their role in the tumor development differs depending on their cellular origin. The mechanism of Cts action in cancer is not limited only by their proteolytic action. The Cts influence on signal transduction pathways associated with cancer development, including the pathway involving growth factors, which is mediated through receptors tyrosine kinases (RTK) and various signaling mitogen-activated protein kinases (MAPK), has been proven. In addition, Cts are able to promote the epithelial-mesenchymal transition (EMT) by activating signal transduction pathways such as Wnt, Notch, and the pathway involving TGF-β. So, Ctc perform specific both destructive and regulatory functions, carrying out proteolysis, both inside and outside the cell.

scholarly journals Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ajaz A. Bhat ◽  
Sabah Nisar ◽  
Selma Maacha ◽  
Tatiana Correa Carneiro-Lobo ◽  
Sabah Akhtar ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Growth Factors ◽  
Intracellular Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Distant Metastases ◽  
Cell Types ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Mesenchymal Transition ◽  
Wide Range

AbstractEsophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases among patients with advanced disease account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, and growth factors, which play a significant role in supporting the growth and aggressive behavior of cancer cells. The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. The molecular changes in the TME are used as biological markers for diagnosis, prognosis, and response to treatment in patients. This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development. In addition, it discusses the wide range of changes and intracellular signaling pathways that occur in the TME. Overall, this is a relatively unexplored field that could provide crucial insights into tumor immunology and encourage the effective application of modulatory cytokine-chemokine therapy to EC.

Sign in / Sign up

Export Citation Format

Share Document