scholarly journals Functional Interaction of E1AF and Sp1 in Glioma Invasion

2007 ◽  
Vol 27 (24) ◽  
pp. 8770-8782 ◽  
Author(s):  
Jianhai Jiang ◽  
Yuanyan Wei ◽  
Jialin Shen ◽  
Dan Liu ◽  
Xiaoning Chen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Functional Interaction ◽  
Glioma Invasion ◽  
Cooperative Effort ◽  
Binding Partner ◽  
Sp1 Transcription Factor ◽  
Epidermal Growth ◽  
First Time

ABSTRACT Transcription factor E1AF is widely known to play critical roles in tumor metastasis via directly binding to the promoters of genes involved in tumor migration and invasion. Here, we report for the first time E1AF as a novel binding partner for ubiquitously expressed Sp1 transcription factor. E1AF forms a complex with Sp1, contributes to Sp1 phosphorylation and transcriptional activity, and functions as a mediator between epidermal growth factor and Sp1 phosphorylation and activity. Sp1 functions as a carrier bringing E1AF to the promoter region, thus activating transcription of glioma-related gene for β1,4-galactosyltransferase V (GalT V; EC 2.4.1.38). Biologically, E1AF functions as a positive invasion regulator in glioma in cooperation with Sp1 partly via up-regulation of GalT V. This report describes a new mechanism of glioma invasion involving a cooperative effort between E1AF and Sp1 transcription factors.

scholarly journals Anti-Metastasis Fascin Inhibitors Decrease the Growth of Specific Subtypes of Cancers

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2287 ◽  
Author(s):  
Yufeng Wang ◽  
J. Jillian Zhang ◽  
Xin-Yun Huang
Keyword(s):  
B Cell ◽  
Tumor Metastasis ◽  
Growth Factor Receptor ◽  
B Cell Lymphoma ◽  
Migration And Invasion ◽  
Tumor Cell Migration ◽  
Elevated Expression ◽  
Cancer Types ◽  
Epidermal Growth

Fascin is an actin-bundling protein that is critical for filopodial formation and other cellular cytoskeletal structures. An elevated expression of fascin has been observed in tumor cells and is correlated with a shorter survival of cancer patients. Given its roles in tumor cell migration and invasion, we have developed small-molecule fascin inhibitors to prevent and delay tumor metastasis. Here we report the characterization of a new fascin inhibitor in mice. In addition to its inhibitory effects on tumor metastasis, we also report that fascin inhibitors can decrease the growth of specific subtypes of cancers, including epidermal growth factor receptor (EGFR)-high triple-negative breast cancer, and activated B-cell subtypes of diffuse large B-cell lymphoma. Hence, fascin inhibitors can be used to not only inhibit tumor metastasis, but also decrease the tumor growth of specific cancer types.

scholarly journals IFN-γ-response mediator GBP-1 represses human cell proliferation by inhibiting the Hippo signaling transcription factor TEAD

2018 ◽  
Vol 475 (18) ◽  
pp. 2955-2967 ◽  
Author(s):  
Bea Unterer ◽  
Veit Wiesmann ◽  
Mekala Gunasekaran ◽  
Heinrich Sticht ◽  
Clara Tenkerian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Migration And Invasion ◽  
Hippo Signaling ◽  
Inhibition Of Proliferation ◽  
Molecular Modeling Studies ◽  
Ifn Γ ◽  
Inhibitory Domain ◽  
Tumorigenic Activity ◽  
First Time

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts important functions in inflammation, infectious diseases, and cancer. The large GTPase human guanylate-binding protein 1 (GBP-1) is among the most strongly IFN-γ-induced cellular proteins. Previously, it has been shown that GBP-1 mediates manifold cellular responses to IFN-γ including the inhibition of proliferation, spreading, migration, and invasion and through this exerts anti-tumorigenic activity. However, the mechanisms of GBP-1 anti-tumorigenic activities remain poorly understood. Here, we elucidated the molecular mechanism of the human GBP-1-mediated suppression of proliferation by demonstrating for the first time a cross-talk between the anti-tumorigenic IFN-γ and Hippo pathways. The α9-helix of GBP-1 was found to be sufficient to inhibit proliferation. Protein-binding and molecular modeling studies revealed that the α9-helix binds to the DNA-binding domain of the Hippo signaling transcription factor TEA domain protein (TEAD) mediated by the 376VDHLFQK382 sequence at the N-terminus of the GBP-1-α9-helix. Mutation of this sequence resulted in abrogation of both TEAD interaction and suppression of proliferation. Further on, the interaction caused inhibition of TEAD transcriptional activity associated with the down-regulation of TEAD-target genes. In agreement with these results, IFN-γ treatment of the cells also impaired TEAD activity, and this effect was abrogated by siRNA-mediated inhibition of GBP-1 expression. Altogether, this demonstrated that the α9-helix is the proliferation inhibitory domain of GBP-1, which acts independent of the GTPase activity through the inhibition of the Hippo transcription factor TEAD in mediating the anti-proliferative cell response to IFN-γ.

scholarly journals Hypoxia-Inducible Factor 1A Upregulates HMGN5 by Increasing the Expression of GATA1 and Plays a Role in Osteosarcoma Metastasis

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Enjie Xu ◽  
Zhe Ji ◽  
Heng Jiang ◽  
Tao Lin ◽  
Jun Ma ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Metastasis ◽  
Malignant Tumors ◽  
Hypoxia Inducible Factor ◽  
High Mobility ◽  
Migration And Invasion ◽  
Hypoxic Environment ◽  
The Relationship ◽  
Selection Of ◽  
Cells Cultured

Osteosarcoma is one of the most common malignant tumors in children and adolescents and is characterized by early metastasis. High-mobility group N (HMGN) domains are involved in the development of several tumors. Our previous study found that HMGN5 is highly expressed in osteosarcoma tissues and knockdown of HMGN5 inhibits migration and invasion of U-2 OS and Saos-2 cells. A hypoxic environment is commonly found in solid tumors such as osteosarcoma and is likely to be associated with tumor metastasis, so we further explored the relationship between HMGN5 and the hypoxic environment. Hypoxia-inducible factor 1A (HIF1A) is an adaptive factor in the hypoxic environment. We found that HIF1A and HMGN5 were upregulated in osteosarcoma (OS) cells cultured in the hypoxic environment, and the results of overexpression and knockdown experiments showed that HIF1A upregulated the transcription factor GATA1 and further promoted the expression of HMGN5. In addition, MMP2 and MMP9 were subsequently upregulated through the c-jun pathway, and finally, this promoted the migration and invasion of OS cells. It is suggested that HMGN5 may be an important downstream factor for HIF1A to promote osteosarcoma metastasis. It has an important clinical significance for the selection of therapeutic targets for osteosarcoma.

scholarly journals Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xuexiu Zhang ◽  
Jianning Yao ◽  
Haoling Shi ◽  
Bing Gao ◽  
Haining Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Sp1 Transcription Factor ◽  
Reporter Assays ◽  
Sphere Formation

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

scholarly journals Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen Hang ◽  
Shanojie Zhao ◽  
Tiejun Wang ◽  
Yan Zhang
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Nuclear Accumulation ◽  
Migration And Invasion ◽  
Ubiquitin Protein Ligase ◽  
Novel Target ◽  
First Time ◽  
Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

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