Targeting EphA2 in cancer

Xiao, Ta; Xiao, Yuhang; Wang, Wenxiang; Tang, Yan; Xiao, Zhi‐Qiang; Su, Min

doi:10.1186/s13045-020-00944-9

Cited by 106 publications

(85 citation statements)

References 113 publications

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“…As an oncogenic biomarker, EphA2 is associated with the poor prognosis of a variety of malignant tumors ( Ieguchi and Maru, 2019 ). 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 ).…”

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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“…In contrast, inhibition of EphB4 signaling was not effective in FN-RMS, but demonstrated a decrease in tumor progression in a murine model of FP-RMS, suggesting that inhibition of EphB4 may be more effective when evaluated in combination with other agents [ 122 ]. Inhibitors of Eph/ephrin have been studied in clinical trials in adults with solid tumors, but these agents have not been studied in patients with RMS [ 118 , 123 , 124 ].…”

Section: Other Targeted Agentsmentioning

confidence: 99%

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

Pacenta

Allen‐Rhoades

Langenau

et al. 2021

JCM

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Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children’s Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.

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“…The widely studied Eph in cancer, EphA2, has been proposed as therapeutic target in OC, albeit none of the reported strategies have provided promising results in clinical trials 27 . Upon interaction with ephrinA ligand, EphA2 transphosphorylation at specific cytoplasmic tyrosine residues leads to the receptor activation, followed by internalization of the receptor-ligand complex and eventually receptor degradation or dephosphorylation 12 , 28 .…”

Section: Introductionmentioning

confidence: 99%

Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality

Jukonen

Moyano‐Galceran

Höpfner

et al. 2021

Sci Rep

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Erythropoietin producing hepatocellular (Eph) receptors and their membrane-bound ligands ephrins are variably expressed in epithelial cancers, with context-dependent implications to both tumor-promoting and -suppressive processes in ways that remain incompletely understood. Using ovarian cancer tissue microarrays and longitudinally collected patient cells, we show here that ephrinA5/EFNA5 is specifically overexpressed in the most aggressive high-grade serous carcinoma (HGSC) subtype, and increased in the HGSC cells upon disease progression. Among all the eight ephrin genes, high EFNA5 expression was most strongly associated with poor overall survival in HGSC patients from multiple independent datasets. In contrast, high EFNA3 predicted improved overall and progression-free survival in The Cancer Genome Atlas HGSC dataset, as expected for a canonical inducer of tumor-suppressive Eph receptor tyrosine kinase signaling. While depletion of either EFNA5 or the more extensively studied, canonically acting EFNA1 in HGSC cells increased the oncogenic EphA2-S897 phosphorylation, EFNA5 depletion left unaltered, or even increased the ligand-dependent EphA2-Y588 phosphorylation. Moreover, treatment with recombinant ephrinA5 led to limited EphA2 tyrosine phosphorylation, internalization and degradation compared to ephrinA1. Altogether, our results suggest a unique function for ephrinA5 in Eph-ephrin signaling and highlight the clinical potential of ephrinA5 as a cell surface biomarker in the most aggressive HGSCs.

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Targeting EphA2 in cancer

Cited by 106 publications

References 113 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

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality

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