Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast

Mitra, Debolina; Bhattacharyya, Sayantan; Alam, Neyaz; Sen, Sagar; Mitra, Saunak; Mandal, Santosh K.; Vignesh, S.; Majumder, Biswanath; Murmu, Nabendu

doi:10.1007/s10549-019-05482-8

Cited by 31 publications

(24 citation statements)

References 53 publications

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“…Recent studies suggest that EphA2 is involved in tumor invasion, angiogenesis, tumor matrix degradation and tumor cell adhesion (Xiao et al, 2020). A series of studies have shown that EphA2 is associated with vascular mimicry in breast cancer, gastric cancer and prostate cancer (Li et al, 2018;Kim et al, 2019a;Kim et al, 2019b;Yeo et al, 2019;Mitra et al, 2020). However, few studies have focused on the role of EphA2 in vascular mimicry of HCC (Li et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis

et al. 2021

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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 26 compounds 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 (Data are available via ProteomeXchange with identifier PXD022203). 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.

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Section: Introductionmentioning

confidence: 99%

COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis

et al. 2021

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“…Instantaneous knockout of EphA2 in aggressive melanoma cells abrogates tubular structure formation in these tumor cells (Hendrix et al, 2003). Recently, EphA2 expression has been reported to be significantly correlated with VM and to contribute to poor prognosis in breast cancer patients (Mitra et al, 2019). VE-cadherin and EphA2 are both over-expressed in glioma, playing vital roles in VM network formation by promoting extracellular matrix remodeling (Wykosky et al, 2005;Wu et al, 2011;Mao et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Celastrol Suppresses Glioma Vasculogenic Mimicry Formation and Angiogenesis by Blocking the PI3K/Akt/mTOR Signaling Pathway

Zhu¹,

Liu²,

Zhao³

et al. 2020

Front. Pharmacol.

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Angiogenesis and vasculogenic mimicry (VM) are thought to be the predominant processes ensuring tumor blood supply during the growth and metastasis of glioblastoma (GBM). Celastrol has potential anti-glioma effects, however the mechanisms underlying these effects remain unclarified. Recent studies have shown that the PI3K/Akt/mTOR signaling pathway is closely related to angiogenesis and VM formation. In the present study, we have demonstrated, for the first time, that celastrol eliminated VM formation by blocking this signaling pathway in glioma cells. By the treatment of celastrol, tumor growth was suppressed, tight junction and basal lamina structures in tumor microvasculature were disarranged in U87 glioma orthotopic xenografts in nude mice. Periodic acid Schiff (PAS)-CD31 staining revealed that celastrol inhibited both VM and angiogenesis in tumor tissues. Additionally, celastrol reduced the expression levels of the angiogenesis-related proteins CD31, vascular endothelial growth factor receptor (VEGFR) 2, angiopoietin (Ang) 2 and VEGFA, VM-related proteins ephrin type-A receptor (EphA) 2, and vascular endothelial (VE)-cadherin. Hypoxia inducible factor (HIF)-1a, phosphorylated PI3K, Akt, and mTOR were also downregulated by treatment with celastrol. In vitro, we further demonstrated that celastrol inhibited the growth, migration, and invasion of U87 and U251 cells, disrupted VM formation, and blocked the activity of PI3K, Akt, and mTOR. Collectively, our data suggest that celastrol inhibits VM formation and angiogenesis likely by regulating the PI3K/Akt/mTOR signaling pathway.

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“…VE-cadherin also mediates the activities of EphA2, a member of the ephrin-receptor family of PTKs, which is crucial for angiogenesis [39]. Mitra et al, recently found that phosphorylation of EphA2 was signi cantly associated with the occurrence of VM in invasive breast carcinoma [40]. Co-localization of VE-cadherin with EphA2 is reported to induce the activation of MMPs, resulting in matrix remodeling and VM channel formation [12,15,41].…”

Section: Discussionmentioning

confidence: 99%

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma

Hong

Yoon

et al. 2020

Preprint

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Background : Vasculogenic mimicry (VM) is the formation of an alternative circulatory system by aggressive tumor cells. The characteristics of VM and its underlying mechanism in oral squamous cell carcinoma (OSCC) remain unclear. This study aims to determine the relationship between VM channels in OSCC tissues and clinical outcomes and to investigate the biological role of SOX7 in VM in OSCC cells. Methods : CD31/PAS double staining was performed to evaluate VM status in OSCC tissue. The relationships between VM and clinicopathological variables, and VM and SOX7 levels were analyzed. VM channel formation was assay performed to observe VM channels in the OSCC cell lines. To investigate the role of SOX7 in VM channel formation, SOX7 was transiently over-expressed in SCC-9 cells. VM-modulating genes were identified by Western blotting. Results : We confirmed the presence of VM channels in OSCC tissue and several cell lines and found a positive correlation between VM and lymph node metastasis and patient survival in OSCC ( P = 0.003). We also found that the presence of VM channels in OSCC tissue was inversely associated with SOX7 expression ( P = 0.020). We observed that overexpression of SOX7 impaired VM channel formation by reducing the expression of VE-cadherin, thereby inhibiting cell migration and invasion. Conclusion : These results suggest that SOX7 plays an important role in the regulation of VM channel formation and may inhibit OSCC metastasis.

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Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast

Cited by 31 publications

References 53 publications

COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis

COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis

Celastrol Suppresses Glioma Vasculogenic Mimicry Formation and Angiogenesis by Blocking the PI3K/Akt/mTOR Signaling Pathway

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma

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