scholarly journals The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells

2010 ◽  
Vol 120 (2) ◽  
pp. 533-544 ◽  
Author(s):  
Romaine I. Fernando ◽  
Mary Litzinger ◽  
Paola Trono ◽  
Duane H. Hamilton ◽  
Jeffrey Schlom ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Mesenchymal Transition ◽  
T Box

scholarly journals TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition

Oncogene ◽  
2007 ◽  
Vol 27 (18) ◽  
pp. 2635-2647 ◽  
Author(s):  
H Jung ◽  
K P Lee ◽  
S J Park ◽  
J H Park ◽  
Y-s Jang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Mesenchymal Transition

scholarly journals Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances

2020 ◽  
Vol 8 (1) ◽  
pp. e000433 ◽  
Author(s):  
Hanne Lind ◽  
Sofia R Gameiro ◽  
Caroline Jochems ◽  
Renee N. Donahue ◽  
Julius Strauss ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Checkpoint Inhibitors ◽  
Human Tumor ◽  
Chemotherapeutic Agents ◽  
Human Tumor Cells ◽  
Human Carcinoma ◽  
Mesenchymal Transition

Immunosuppressive entities in the tumor microenvironment (TME) remain a major impediment to immunotherapeutic approaches for a majority of patients with cancer. While the immunosuppressive role of transforming growth factor-β (TGF-β) in the TME is well known, clinical studies to date with anti-TGF-β agents have led to limited success. The bifunctional agent bintrafusp alfa (previously designated M7824) has been developed in an attempt to address this issue. Bintrafusp alfa consists of an IgG1targeting programmed death ligand 1 (PD-L1) moiety fused via peptide linkers to the extracellular domain of two TGF-β receptor II molecules designed to ‘trap’ TGF-β in the TME. This agent is able to bring the TGF-β trap to the TME via its anti-PD-L1 component, thus simultaneously attacking both the immunosuppressive PD-L1 and TGF-β entities. A number of preclinical studies have shown bintrafusp alfa capable of (1) preventing or reverting TGF-β-induced epithelial-mesenchymal transition in human carcinoma cells; this alteration in tumor cell plasticity was shown to render human tumor cells more susceptible to immune-mediated attack as well as to several chemotherapeutic agents; (2) altering the phenotype of natural killer and T cells, thus enhancing their cytolytic ability against tumor cells; (3) mediating enhanced lysis of human tumor cells via the antibody-dependent cell-mediated cytotoxicity mechanism; (4) reducing the suppressive activity of Tregcells; (5) mediating antitumor activity in numerous preclinical models and (6) enhancing antitumor activity in combination with radiation, chemotherapy and several other immunotherapeutic agents. A phase I clinical trial demonstrated a safety profile similar to other programmed cell death protein 1 (PD-1)/PD-L1 checkpoint inhibitors, with objective and durable clinical responses. We summarize here preclinical and emerging clinical data in the use of this bispecific and potentially multifunctional agent.

scholarly journals The T Box Transcription Factor TBX2 Promotes Epithelial-Mesenchymal Transition and Invasion of Normal and Malignant Breast Epithelial Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41355 ◽  
Author(s):  
Bin Wang ◽  
Linsey E. Lindley ◽  
Virneliz Fernandez-Vega ◽  
Megan E. Rieger ◽  
Andrew H. Sims ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Epithelial Cells ◽  
Mesenchymal Transition ◽  
T Box ◽  
Malignant Breast ◽  
Breast Epithelial

scholarly journals Development of Cancer Vaccines Targeting Brachyury, a Transcription Factor Associated with Tumor Epithelial-Mesenchymal Transition

2017 ◽  
Vol 203 (2) ◽  
pp. 128-138 ◽  
Author(s):  
Duane H. Hamilton ◽  
Justin M. David ◽  
Charli Dominguez ◽  
Claudia Palena
Keyword(s):  
Transcription Factor ◽  
Cancer Vaccines ◽  
Epithelial Mesenchymal Transition ◽  
Human Tumor ◽  
Tumor Resistance ◽  
Epithelial Cancer ◽  
Immune Effector ◽  
Mesenchymal Transition ◽  
Immune Mediated ◽  
Tumor Dissemination

Epithelial-mesenchymal transition (EMT) is recognized as a relevant process during the progression of carcinomas towards metastatic disease. Epithelial cancer cells undergoing an EMT program may acquire mesenchymal features, motility, invasiveness, and resistance to a variety of anticancer therapeutics. Preventing or reverting the EMT process in carcinomas has the potential to minimize tumor dissemination and the emergence of therapeutic resistance. One of the strategies currently under investigation to target tumor cells undergoing EMT is the generation of a sustained immune response directed against an essential molecular driver of the process. This review focuses on the current development of immune-mediated anticancer interventions aimed at targeting a transcription factor, brachyury, associated with human tumor EMT. Also presented here is a summary of recent studies demonstrating a role for EMT in tumor resistance to immune effector cytotoxicity, and the study of novel strategies aimed at reverting the EMT to be used in combination with immune-mediated anticancer interventions.

Modified DNA fragments specifically and irreversibly bind transcription factor NF-κB in lysates of human tumor cells

2006 ◽  
Vol 71 (4) ◽  
pp. 454-460
Author(s):  
M. A. Timchenko ◽  
E. Yu. Rybalkina ◽  
A. Yu. Lomakin ◽  
K. I. Evlakov ◽  
I. N. Serdyuk ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Cells ◽  
Human Tumor ◽  
Dna Fragments ◽  
Human Tumor Cells ◽  
Modified Dna

scholarly journals Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 521
Author(s):  
Ashish Kumar-Singh ◽  
Malgorzata Maria Parniewska ◽  
Nikolina Giotopoulou ◽  
Joman Javadi ◽  
Wenwen Sun ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cells ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Human Tumor ◽  
Surface Adhesion ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Cadherin Switch ◽  
Plastic Process

Tumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not fully understood. Syndecan-1 (SDC1) is the major cell surface proteoglycan in epithelial cells and has been shown to regulate carcinoma progression and EMT. Recently, it was discovered that SDC1 translocates into the cell nucleus in certain tumor cells. Nuclear SDC1 inhibits cell proliferation, but whether nuclear SDC1 contributes to the regulation of EMT is not clear. Here, we report that loss of nuclear SDC1 is associated with cellular elongation and an E-cadherin-to-N-cadherin switch during TGF-β1-induced EMT in human A549 lung adenocarcinoma cells. Further studies showed that nuclear translocation of SDC1 contributed to the repression of mesenchymal and invasive properties of human B6FS fibrosarcoma cells. The results demonstrate that nuclear translocation contributes to the capacity of SDC1 to regulate epithelial-mesenchymal plasticity in human tumor cells and opens up to mechanistic studies to elucidate the mechanisms involved.

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