scholarly journals Regulation of TEAD Transcription Factors in Cancer Biology

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 600 ◽  
Author(s):  
Hyunbin Huh ◽  
Dong Kim ◽  
Han-Sol Jeong ◽  
Hyun Park
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Tumor Progression ◽  
Transforming Growth Factor Beta ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Transforming Growth Factor ◽  
Clinicopathological Parameters ◽  
Transcriptional Output

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

scholarly journals Transforming Growth Factor Beta has Dual Effects on MMP9 and uPA Expression in HTR-8/SVneo Human Trophoblastic Cell Line

2019 ◽  
Vol 24 (1) ◽  
pp. 26-37
Author(s):  
Sandra Susana Novoa Herran ◽  
Mariela Castelblanco ◽  
Myriam Sanchez-Gomez ◽  
Adriana Umaña Pérez
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
In Silico ◽  
Transforming Growth Factor ◽  
In Silico Analysis ◽  
Negative Regulator ◽  
Trophoblast Invasion ◽  
Trophoblastic Cell ◽  
Growth Factor Beta

Invasion of trophoblast into endometrium is vital for successful pregnancy development. MMP9 and uPA are key proteases in this process, but it is still not clear the regulation of its expression by Transforming Growth Factor Beta (TGF-β), known negative regulator of trophoblast invasion. We evaluated the effect of TGF-β on the transcriptional expression of uPA and MMP9 over time, in HTR- /SVneo trophoblast cells cultured with or without 0.5 % fetal bovine serum, via RT qPCR. The involved transcription factors and signaling pathways were analyzed in silico, using Proscan, Enrich, PCViz and WikiPathway. Results showed that that TGF-β regulates the expression of uPA and MMP9. Serum modified the nature of TGF-β’s effects on uPA expression, from negative without serum to positive with it, showing opposite effects on MMP9 expression. In silico analysis evidenced different transcription factors for each protease, some belonging to TGF-β ssignaling pathway, and crosstalk with MAPK and Wnt/β-catenin pathways. The TGF-β ddual role is discussed proposing that serum affects the cellular context. Transcriptional regulation of MMP9 and uPA by TGF-β is differential and depends on serum presence and evaluation time.

scholarly journals Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers

2021 ◽  
Vol 22 (24) ◽  
pp. 13181
Author(s):  
Jinwook Chung ◽  
Md Nazmul Huda ◽  
Yoonhwa Shin ◽  
Sunhee Han ◽  
Salima Akter ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Antioxidant Systems ◽  
Growth Factor Beta

The downregulation of reactive oxygen species (ROS) facilitates precancerous tumor development, even though increasing the level of ROS can promote metastasis. The transforming growth factor-beta (TGF-β) signaling pathway plays an anti-tumorigenic role in the initial stages of cancer development but a pro-tumorigenic role in later stages that fosters cancer metastasis. TGF-β can regulate the production of ROS unambiguously or downregulate antioxidant systems. ROS can influence TGF-β signaling by enhancing its expression and activation. Thus, TGF-β signaling and ROS might significantly coordinate cellular processes that cancer cells employ to expedite their malignancy. In cancer cells, interplay between oxidative stress and TGF-β is critical for tumorigenesis and cancer progression. Thus, both TGF-β and ROS can develop a robust relationship in cancer cells to augment their malignancy. This review focuses on the appropriate interpretation of this crosstalk between TGF-β and oxidative stress in cancer, exposing new potential approaches in cancer biology.

scholarly journals It Takes Two to Tango: Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1965 ◽  
Author(s):  
Christian Hiepen ◽  
Paul-Lennard Mendez ◽  
Petra Knaus
Keyword(s):  
Shear Stress ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Research Field ◽  
Bmp Signaling ◽  
Growth Factor Signaling ◽  
Mechanical Stimuli ◽  
Signaling Crosstalk

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGFβ) superfamily of cytokines. While some ligand members are potent inducers of angiogenesis, others promote vascular homeostasis. However, the precise understanding of the molecular mechanisms underlying these functions is still a growing research field. In bone, the tissue in which BMPs were first discovered, crosstalk of TGFβ/BMP signaling with mechanobiology is well understood. Likewise, the endothelium represents a tissue that is constantly exposed to multiple mechanical triggers, such as wall shear stress, elicited by blood flow or strain, and tension from the surrounding cells and to the extracellular matrix. To integrate mechanical stimuli, the cytoskeleton plays a pivotal role in the transduction of these forces in endothelial cells. Importantly, mechanical forces integrate on several levels of the TGFβ/BMP pathway, such as receptors and SMADs, but also global cell-architecture and nuclear chromatin re-organization. Here, we summarize the current literature on crosstalk mechanisms between biochemical cues elicited by TGFβ/BMP growth factors and mechanical cues, as shear stress or matrix stiffness that collectively orchestrate endothelial function. We focus on the different subcellular compartments in which the forces are sensed and integrated into the TGFβ/BMP growth factor signaling.

Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation

1989 ◽  
Vol 9 (3) ◽  
pp. 1255-1262
Author(s):  
L Pertovaara ◽  
L Sistonen ◽  
T J Bos ◽  
P K Vogt ◽  
J Keski-Oja ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Base Line ◽  
Tgf Beta ◽  
Early Effect ◽  
Growth Factor Beta

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.

scholarly journals P.106 Thrombospondin 1 mediates transforming growth factor beta induced premature senescence in primary glioblastoma cells

2016 ◽  
Vol 43 (S2) ◽  
pp. S45-S45
Author(s):  
R Kumar ◽  
I Lorimer
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Global Gene Expression ◽  
Premature Senescence ◽  
Primary Glioblastoma ◽  
Thrombospondin 1 ◽  
Growth Factor Beta ◽  
Novel Therapeutic Strategies

Background: Glioblastoma is the most common primary malignant brain tumor. Primary Glioblastoma (PriGO) cells are key drivers of glioblastoma. Senescence is the irreversible growth arrest of cells with continued metabolic activity. Recently, I discovered PriGO cells undergo premature senescence in response to Fetal Bovine Serum (FBS). Determining the underlying molecular mechanisms may allow development of novel therapeutic strategies to decrease the malignant potential of glioblastoma. Methods: Global gene expression changes in PriGO cells treated with serum were analyzed and compared to untreated cells. Senescence was determined by the Senescence-Associated-Beta-Galactosidase (SA-B-Gal) assay. Results: PriGO cells treated with serum demonstrated increased expression of genes in the Transforming Growth Factor Beta (TGF-B) pathway, such as Thrombospondin 1 (TSP1), compared to untreated cells. TGF-B treatment of PriGO cells significantly increased senescence compared to untreated cells. Treatment of PriGO cells with serum and the TGF-B inhibitor SB431542 led to a decrease in senescence compared to serum only treated cells. Treatment of PriGO cells with serum and the TSP1 inhibitor LSKL led to a reduction in senescence compared to serum only treated cells. Conclusions: Our data identifies TGF-B as an important component of serum responsible for inducing senescence in PriGO cells. Furthermore, TGF-B induced senescence in PriGO cells is in part mediated by TSP1.

scholarly journals Pericyte-Endothelial Interactions in the Retinal Microvasculature

2020 ◽  
Vol 21 (19) ◽  
pp. 7413
Author(s):  
Hu Huang
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Neurovascular Unit ◽  
Blood Retinal Barrier ◽  
Vascular Disorders ◽  
Pathological Conditions ◽  
Retinal Microvasculature

Retinal microvasculature is crucial for the visual function of the neural retina. Pericytes and endothelial cells (ECs) are the two main cellular constituents in the retinal microvessels. Formation, maturation, and stabilization of the micro-vasculatures require pericyte-endothelial interactions, which are perturbed in many retinal vascular disorders, such as retinopathy of prematurity, retinal vein occlusion, and diabetic retinopathy. Understanding the cellular and molecular mechanisms of pericyte-endothelial interaction and perturbation can facilitate the design of therapeutic intervention for the prevention and treatment of retinal vascular disorders. Pericyte-endothelial interactions are indispensable for the integrity and functionality of retinal neurovascular unit (NVU), including vascular cells, retinal neurons, and glial cells. The essential autocrine and paracrine signaling pathways, such as Vascular endothelial growth factor (VEGF), Platelet-derived growth factor subunit B (PDGFB), Notch, Angipointein, Norrin, and Transforming growth factor-beta (TGF-β), have been well characterized for the regulation of pericyte-endothelial interactions in the neo-vessel formation processes (vasculogenesis and angiogenesis) during embryonic development. They also play a vital role in stabilizing and remodeling mature vasculature under pathological conditions. Awry signals, aberrant metabolisms, and pathological conditions, such as oxidative stress and inflammation, can disrupt the communication between pericytes and endothelial cells, thereby resulting in the breakdown of the blood-retinal barrier (BRB) and other microangiopathies. The emerging evidence supports extracellular exosomes’ roles in the (mis)communications between the two cell types. This review summarizes the essential knowledge and updates about new advancements in pericyte-EC interaction and communication, emphasizing the retinal microvasculature.

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