Novel role for tumor suppressor gene, liver kinase B1, in epithelial mesenchymal transition leading to chronic lung allograft dysfunction

2021 ◽  
Author(s):  
Mohammad Rahman ◽  
Ranjithkumar Ravichandran ◽  
Sandhya Bansal ◽  
Kristina Sanborn ◽  
Sara Bowen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Mesenchymal Transition ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Liver Kinase B1

Wt1-expressing progenitors contribute to multiple tissues in the developing lung

2013 ◽  
Vol 305 (4) ◽  
pp. L322-L332 ◽  
Author(s):  
Elena Cano ◽  
Rita Carmona ◽  
Ramón Muñoz-Chápuli
Keyword(s):  
Smooth Muscle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Fluorescent Protein ◽  
Wilms Tumor ◽  
Yellow Fluorescent Protein ◽  
Suppressor Gene ◽  
Differentiation Potential ◽  
Mesenchymal Transition ◽  
Lung Morphogenesis

Lungs develop from paired endodermal outgrowths surrounded by a mesodermal mesenchyme. Part of this mesenchyme arises from epithelial-mesenchymal transition of the mesothelium that lines the pulmonary buds. Previous studies have shown that this mesothelium-derived mesenchyme contributes to the smooth muscle of the pulmonary vessels, but its significance for lung morphogenesis and its developmental fate are still little known. We have studied this issue using the transgenic mouse model mWt1/IRES/GFP-Cre (Wt1cre) crossed with the Rosa26R-EYFP reporter mouse. In the developing lungs, Wt1, the Wilms' tumor suppressor gene, is specifically expressed in the embryonic mesothelium. In the embryos obtained from the crossbreeding, the Wt1-expressing cell lineage produces the yellow fluorescent protein (YFP), allowing for colocalization with differentiation markers. Wt1cre-YFP cells were very abundant from the origin of the lung buds to postnatal stages, contributing significantly to pulmonary endothelial and smooth muscle cells, bronchial musculature, tracheal and bronchial cartilage, as well as CD34+ fibroblast-like interstitial cells. Thus Wt1cre-YFP mesenchymal cells show the very same differentiation potential as the splanchnopleural mesenchyme surrounding the lung buds. FSP1+ fibroblast-like cells were always YFP−; they expressed the common leukocyte antigen CD45 and were apparently recruited from circulating progenitors. We have also found defects in pulmonary development in Wt1−/− embryos, which showed abnormally fused lung lobes, round-shaped and reduced pleural cavities, and diaphragmatic hernia. Our results suggest a novel role for the embryonic mesothelium-derived cells in lung morphogenesis and involve the Wilms' tumor suppressor gene in the development of this organ.

Epithelial-mesenchymal transition in chronic lung allograft dysfunction. Role of leucocyte microparticles

2016 ◽  
Author(s):  
Benjamin Renaud-Picard ◽  
Justine Toussaint ◽  
Fatiha El Ghazouani ◽  
Florence Toti ◽  
Laurence Kessler ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction

scholarly journals Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial–mesenchymal transition and metastasis

2017 ◽  
Vol 8 (6) ◽  
pp. e2838-e2838 ◽  
Author(s):  
Ting Zhang ◽  
Ping Yin ◽  
Zichen Zhang ◽  
Banglao Xu ◽  
Di Che ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Pigment Epithelium ◽  
Suppressor Gene ◽  
Mesenchymal Transition ◽  
Pigment Epithelium Derived Factor ◽  
Epithelial Phenotype

AbstractDistant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial–mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features. The knockdown of PEDF induced EMT in lower metastatic NPC cell lines and overexpression of PEDF restored epithelial phenotype in higher metastatic NPC cell lines with typical EMT. The inhibition of PEDF mediated NPC cell spontaneous metastasisin vivo. LRP6/GSK3β/β-catenin signal pathway rather than AKT/GSK3βpathway was involved in the effects of PEDF on EMT. The expression of PEDF was directly downregulated by elevated miR-320c in NPC. In conclusion, our findings indicate for the first time that PEDF functions as tumor-suppressor gene in the occurrence of EMT and metastasis in NPC. PEDF could serve as a promising candidate for NPC diagnosis, prognosis and treatment.

scholarly journals MiR-30c Plays Diagnostic and Prognostic Roles and Mediates Epithelial–mesenchymal Transition (EMT) and Proliferation of Glioma by Affecting Notch1

2021 ◽  
Author(s):  
Mengkao Li ◽  
Wenzhi Liu ◽  
Jin Xu
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Normal Brain ◽  
Who Grade ◽  
Mesenchymal Transition

Abstract miR-30c functions as a tumor suppressor gene in the majority of tumors, including glioma. In our study, we discovered that the expression levels of miR-30c in glioma tissues and plasma prior to operation were lower than that in normal brain tissue following brain injury decompression and plasma in healthy volunteers. The low expression of miR-30c was closely aligned with WHO grade, tumor size, PFS, and OS. Additionally, the miR-30c expression level of tumor tissue was positively correlated with the levels found in preoperative plasma. In cell biology experiments, miR-30c was discovered to inhibit EMT, proliferation, migration, and the invasion of glioma cells. The database of miRNAs target genes, real-time quantitative PCR, western blot, and dual luciferase reporter assay demonstrated that Notch1 is the direct target gene of miR-30c. The inhibitor and shRNA-Notch1 were cotransfected into glioma cells, which illustrated that shRNA-Notch1 could reduce the enhancement of inhibitors in EMT, proliferation, migration, and the invasion of glioma cells. Therefore, we believe that when utilized as a tumor suppressor gene, miR-23a can inhibit EMT, proliferation, migration, and invasion of glioma cells by directly acting on Notch1 at the post-transcriptional level, and it is a potential diagnostic and prognostic marker.

scholarly journals TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

2019 ◽  
Vol 20 (11) ◽  
pp. 2767 ◽  
Author(s):  
Yang Hao ◽  
David Baker ◽  
Peter ten Dijke
Keyword(s):  
Tumor Suppressor ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Suppressor Gene ◽  
Therapeutic Interventions ◽  
Mesenchymal Transition

Transforming growth factor β (TGF-β) is a secreted cytokine that regulates cell proliferation, migration, and the differentiation of a plethora of different cell types. Consistent with these findings, TGF-β plays a key role in controlling embryogenic development, inflammation, and tissue repair, as well as in maintaining adult tissue homeostasis. TGF-β elicits a broad range of context-dependent cellular responses, and consequently, alterations in TGF-β signaling have been implicated in many diseases, including cancer. During the early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inducing cytostasis and the apoptosis of normal and premalignant cells. However, at later stages, when cancer cells have acquired oncogenic mutations and/or have lost tumor suppressor gene function, cells are resistant to TGF-β-induced growth arrest, and TGF-β functions as a tumor promotor by stimulating tumor cells to undergo the so-called epithelial-mesenchymal transition (EMT). The latter leads to metastasis and chemotherapy resistance. TGF-β further supports cancer growth and progression by activating tumor angiogenesis and cancer-associated fibroblasts and enabling the tumor to evade inhibitory immune responses. In this review, we will consider the role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis. In particular, we will highlight recent insights into the multistep and dynamically controlled process of TGF-β-induced EMT and the functions of miRNAs and long noncoding RNAs in this process. Finally, we will discuss how these new mechanistic insights might be exploited to develop novel therapeutic interventions.

scholarly journals Targeting miRNA by tunable small molecule binders: peptidic aminosugar mediated interference in miR-21 biogenesis reverts epithelial to mesenchymal transition

MedChemComm ◽  
2018 ◽  
Vol 9 (7) ◽  
pp. 1147-1154 ◽  
Author(s):  
Arpita Ghosh ◽  
Natalya Degyatoreva ◽  
Casey Kukielski ◽  
Sandra Story ◽  
Sayantan Bhaduri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Small Molecule ◽  
Epithelial To Mesenchymal Transition ◽  
Suppressor Gene ◽  
Mesenchymal Transition ◽  
Malignant Behavior

miR21, a potent regulator of the tumor suppressor gene PTEN, can be silenced to reverse EMT providing an attractive target for abrogating the malignant behavior of breast cancer.

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