Inhibitor of DNA binding-1, a master regulator of vasculogenic mimicry by cancer cells.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1139094 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cancer cells within solid tumours routinely access the blood supply by promoting endothelium-dependent angiogenesis, but tumour vasculature can also be formed by the cancer cells themselves via vasculogenic mimicry (VM). With increasing evidence that VM correlates with cancer progression, understanding the regulatory factors that underpin VM could provide new therapeutic strategies to improve patient outcomes. Herein we investigate changes to the gene expression profile of breast cancer cells during the early stages of VM formation. Results identify the transcriptional regulator Inhibitor of DNA binding 1 (ID1) to be elevated ~10-fold within the first two hours of VM formation by MDA-MB-231-LM2 cells. A role for ID1 in promoting VM was supported by ID1-targeting siRNA in breast and pancreatic cancer cells. Similarly, administration of the pan-ID inhibitor AGX-51, interrupted VM formation by MDA-MB-231-LM2 and BxPC-3 cells. Inhibition of ID1 also reduced the production of pro-angiogenic and pro-cancerous proteins, e.g. DKK-1, VEGF, CD31, MMP9, PDGF-AA, angiogenin, and IL-8. Regulatory control of these genes by ID1 was further implicated through identification of the requisite DNA binding motifs upstream of the gene start site. Finally, in silico analysis of barcoded VM-competent MDA-MB-231 cells injected into the mammary fat pad of mice enabled gene expression profiling of cancer cells in the primary tumour and metastatic sites. Elevated expression of ID1 was observed in the cancer cells that has metastasised to the lung and the liver and was associated with an enrichment of pro-angiogenic genes. Taken together, this study further implicates ID1 as an important master regulator of cancer progression via its role in the formation of VM structures, protein production and metastasis.
2025-06-22 | GSE272838 | GEO
Project description:Vasculogenic mimicry has been generally accepted as a new form of tumor vascularization and regarded as an unfavorable prognostic factor in multiple aggressive malignancies. We previously reported the presence of vasculogenic mimicry in osteosarcoma patients. The mechanistic basis for osteosarcoma VM remains unclear. We used microarrays to detail the global programme of gene expression between 143B cells and HOS cells exposed to Matrigel which showed greatly different vasculogenic mimicry formation potential and identified distinct classes of vasculogenic mimicry-realted genes during this process.
2018-09-15 | GSE119975 | GEO
Project description:Investigating vasculogenic mimicry in breast cancer
| PRJNA971220 | ENA
Project description:Vasculogenic mimicry (VM) is an intriguing phenomenon observed in tumor masses, in which cancer cells organize themselves into capillary-like channels that closely resemble the structure and function of blood vessels. Although VM is believed to contribute to alternative tumor vascularization, the detailed regulatory mechanisms controlling these cellular processes remain poorly understood. Our study aimed to investigate the role of Early Growth Response 1 (EGR1) in regulating VM in aggressive cancer cells, specifically MDA-MB-231 triple-negative breast cancer cells.
2023-08-15 | GSE240489 | GEO
Project description:Erianin abrogates vasculogenic mimicry through targeting m5C methylase NSUN2
| PRJNA1181520 | ENA
Project description:Purpose: The precise temporal and spatial regulation of N5-methylcytosine (m5C) RNA modification plays essential roles in RNA metabolism. Targeting m5C regulation in cancer cells may be a potential strategy for cancer therapy. Erianin is a natural product isolated from Dendrobium chrysotoxum Lindl. Howbeit, the in‐depth understanding of interaction between erianin and m5C modification remains indistinct. Methods: Natural product library screening was used to explore the effects of natural product monomers on uveal melanoma (UM) cells. Intraocular xenografts model was established to examine the effect of erianin. Immunoprecipitation mass spectrometry (IP-MS) and molecular docking analyses were performed to identify NSUN2 as the target of erianin. m5C-meRIP-seq and m5C-meRIP-qPCR analyses were performed to identify the functional target of NSUN2. Tube formation assay and CD31-PAS double staining were used to detect vasculogenic mimicry (VM) in UM. Results: Herein, we report the discovery of erianin as an effective inhibitor of uveal melanoma. Mechanistically, the targeted inhibition of NSUN2 function by erianin results in a decrease in the m5C modification and expression levels of CHAC1 in UM, thereby curtailing the formation of VM. Conclusions: Collectively, our data suggested that erianin significantly inhibited UM progression in vitro and in vivo. Our study unveils a novel therapeutic strategy for combating UM.
2024-12-10 | GSE280936 | GEO
Project description:Gene expression of osteosarcama cell line with vasculogenic mimicry phenotype
| PRJNA490884 | ENA
Project description:Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma cells. In accordance with these observations, CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, respectively. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitor BAY 11-7082. Furthermore, EBV encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 over-expression. Finally, CXCL8 is positively correlated with overall survival in gastric carcinoma patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in gastric carcinoma via NF-κB signaling and CXCL8 may serve as a novel anti-tumor target for EBVaGC.
2021-10-14 | GSE185627 | GEO
Project description:Role of EGR1 in vasculogenic mimicry of MDA-MB-231 cells
| PRJNA1003903 | ENA
Project description:New strategies and drugs are urgently needed to improve the treatment of hepatocellular carcinoma (HCC). Vasculogenic mimicry (VM) has been elucidated being associated with the progression of HCC and anti-VM could be a promising strategy. Celastrus orbiculatus extract (COE), a mixture of 11 terpenoids isolated from the Chinese Herb Celastrus Orbiculatus Vine, has been elucidated to be able to disrupt VM formation in HCC. This study aims to dissect and identify the potential targets of COE on anti-VM formation both in vitro and in vivo that are distinct from our previous study. Proteomics analysis was used to identify differential proteins in HCC cells treated with or without COE. Cells invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation in vitro. RT-PCR and Western Blot were used to examine changes of mRNA and protein respectively. Clinical resected samples were applied to confirm association between VM formation and identified targets. Subcutaneous xenograft tumor model was established to observe tumor growth and VM formation in vivo. PAS-CD34 dual staining was used to detect VM in vivo. A total of 194 proteins were identified to be differentially expressed in HCC cells treated with or without COE. In the 93 down-regulated proteins EphA2 stood out to be regulated on both RNA and protein level. Disruption EphA2 using COE or NVP inhibited VM formation and decreased VM associated biomarkers. In xenograft mouse model, COE inhibited tumor growth and VM formation via down-regulating EphA2. Taken together, our results indicate that COE could be used in HCC treatment because of its promising anti-VM effect.
2021-05-03 | PXD022203 | Pride