Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Wang, Yongcang; Yin, Dengke; Xu, Ge‐Liang; Yu, Wenxia; Quan, Rui-Liang; Zhao, Yajun

doi:10.12659/msm.923409

Cited by 5 publications

(10 citation statements)

References 33 publications

(19 reference statements)

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“…The M2 macrophages are closely correlated with angiogenesis and lymph angiogenesis in cancer [ 45 ]. Importantly, our experiments suggested that NRBP2 overexpression significantly decreased the expression of TME biomarkers IL-6 and VEGFA [ 46 ] in the TPC-1 and CAL62 cells and, and overexpression of NRBP2 in cells reduced the M2 polarization of the co-cultured macrophages. In addition, it was found that the angiogenesis ability of HUVECs was reduced when cultured in an NRBP2 -overexpressing condition.…”

Section: Discussionmentioning

confidence: 99%

GATA binding protein 1 recruits histone deacetylase 2 to the promoter region of nuclear receptor binding protein 2 to affect the tumor microenvironment and malignancy of thyroid carcinoma

Jiang

Chen

et al. 2022

Bioengineered

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The tumor microenvironment (TME) and activated angiogenesis in thyroid carcinoma (TC) are critical for tumor growth and metastasis. Nuclear receptor binding protein 2 ( NRBP2 ) has been suggested as a tumor suppressor. This study examines the function of NRBP2 in the progression of TC and the regulatory mechanism. By analyzing bioinformatic tools including GSE165724 dataset and the Cancer Genome Atlas system, we predicted NRBP2 as a poorly expressed gene in TC. Decreased NRBP2 expression was detected in TC tumor tissues and cells. Poor expression of NRBP2 was linked to unfavorable prognosis of patients. GATA binding protein 1 ( GATA1 ) was found as a negative regulator of NRBP2 . It recruited histone deacetylase2 ( HDAC2 ) to the NRBP2 promoter to trigger histone deacetylation. NRBP2 overexpression suppressed growth of TC cells, and it reduced expression of TME markers, M2 polarization of macrophages, and angiogenesis in TC. Similar results were reproduced in vivo in nude mice. However, the anti-oncogenic roles of NRBP2 were blocked after further overexpression of GATA1 or HDAC2 . In summary, this study demonstrates that GATA1 recruits HDAC2 to the NRBP2 promoter and enhances the TME and angiogenesis in TC cells.

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Section: Discussionmentioning

confidence: 99%

GATA binding protein 1 recruits histone deacetylase 2 to the promoter region of nuclear receptor binding protein 2 to affect the tumor microenvironment and malignancy of thyroid carcinoma

Jiang

Chen

et al. 2022

Bioengineered

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“…In the present study, we identified eight eligible studies consisting of 1079 patients with cancer to evaluate the association between survival and EPHA1 expression in patients with cancer. Wang et al ( 10 , 11 ) and Inokuchi et al ( 8 ) demonstrated that EPHA1 expression was correlated with poor OS in patients with gastric cancer. Toma et al ( 9 ) reported the association between EPHA1 expression and unfavorable OS in clear cell renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…EPHA1 is expressed in various normal tissues such as the intestine, lung, kidney, bladder, and thymus. It is also seen in cancer cells, including colorectal carcinoma, gastric cancer, lung cancer, ovarian carcinoma, renal cell carcinoma, and head and neck squamous cell carcinoma (5)(6)(7)(8)(9)(10)(12)(13)(14)(15). Recent studies have reported that EPHA1 is carcinogenic through interaction with tumor cells as well as interaction with the surrounding tumor microenvironment, and it could also be a potential therapeutic target (10,13,15).…”

Section: Discussionmentioning

confidence: 99%

“…It is also seen in cancer cells, including colorectal carcinoma, gastric cancer, lung cancer, ovarian carcinoma, renal cell carcinoma, and head and neck squamous cell carcinoma (5)(6)(7)(8)(9)(10)(12)(13)(14)(15). Recent studies have reported that EPHA1 is carcinogenic through interaction with tumor cells as well as interaction with the surrounding tumor microenvironment, and it could also be a potential therapeutic target (10,13,15). Moreover, EPHA1 is known to be closely related to the survival of cancer patients (5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these biological functions, EPHA1 is involved in tumor angiogenesis, tumor invasion, and metastasis (2)(3)(4). Moreover, studies show that EPHA1 can not only predict the prognosis of patients with cancer but also serve as a target for cancer treatment (3,(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Original Articlementioning

confidence: 99%

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The association between ephrin receptor-A1 expression and survival in patients with cancer: a meta-analysis

Koh¹,

Jang²,

Lee³

et al. 2022

Transl Cancer Res TCR

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Background Ephrin receptor-A1 (EPHA1) participates in various developmental processes by engaging in cell adhesion, migration, and tissue boundary formation. EPHA1 is also associated with cancer progression and poor prognosis. However, the results of individual studies were inconsistent. Therefore, we aimed to systematically evaluate the association between survival and EPHA1 expression in patients with cancer. Methods We searched electronic databases including PubMed, Embase, Scopus, and the Cochrane library until February 8, 2022. The pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated to explore the relationship between EPHA1 expression and survival in patients with cancer. Funnel plots and Egger’s regression tests were conducted to evaluate publication bias, and sensitivity analysis was performed to determine the reliability of the pooled results. Results Eight studies with 1079 cancer patients were enrolled. EPHA1 expression was associated with progression-free survival (PFS) (HR 1.79, 95% CI: 1.49–2.15, P<0.001). EPHA1 expression was also associated with poor overall survival (HR 2.23, 95% CI: 1.42–3.51, P<0.001), higher tumor stage [odds ratio (OR) 1.74, 95% CI: 1.15–2.61, P=0.008], and lymph node metastasis (OR 1.88, 95% CI: 1.24–2.87, P=0.003) in patients with gastric cancer. Discussion EPHA1 expression was significantly associated with PFS in patients with cancer.

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Erythropoietin-producing hepatocyte kinase receptor A1 facilitating the prgression of SGC-7901 cells and its transplanted tumor by increasing the expression of interleukin-6 and vascular endothelial growth factor in tumor microenvironment

Wang

Zheng

et al. 2022

Eur J Inflamm

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Objectives Many researches showed that Erythropoietin-producing hepatocyte kinase receptor A1 (EphA1) can promote the occurrence and development of malignant tumors and may be related to tumor microenvironment. But most of them are phenomenon studies, and there are few in-depth and complete mechanism studies. This study aims to understand how EphA1 promotes the progression of malignant tumors by regulating tumor microenvironment (focusing on Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF)) from two experimental dimensions of in vitro and in vivo by using genetic engineering technology. Material and Methods We used genetic engineering technology to enhance and knock down EphA1 gene expression in SGC-7901 cells, respectively, and analyzed its influence on cell function and the expression levels of VEGF and IL-6 in cells. Subsequently, we constructed human EphA1 gene overexpression, EphA1 gene silencing, and normal expression of human EphA1 gene subcutaneous transplanted tumor models of SGC-7901 cells nude mice, and analyzed the differences in tumor development and the changes in the expression levels of VEGF and ILl-6 in tumor tissues. Results After EphA1 gene expression was enhanced, the proliferation, invasion and migration of SGC-7901 cells were enhanced, and apoptosis was weakened, and the expression levels of VEGF and IL-6 were increased. While the opposite results were found when EphA1 gene expression were knocked down. Meanwhile, tumor formation time and growth rate of subcutaneous transplantation in nude mice were advanced and the expression levels of VEGF and IL-6 in tumor tissues were increased when EphA1 gene expression were overexpressed by genetic engineering technology. Similarly, the opposite effect occurred in transplanted tumor model when EphA1 gene was silenced. Conclusion Our study showed that EphA1 can up-regulating VEGF and IL-6 expression, thereby enhancing the inflammatory environment and angiogenesis in the tumor microenvironment, and this helps to promote the progression of SGC-7901 cells and its transplanted tumor.

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Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Cited by 5 publications

References 33 publications

GATA binding protein 1 recruits histone deacetylase 2 to the promoter region of nuclear receptor binding protein 2 to affect the tumor microenvironment and malignancy of thyroid carcinoma

GATA binding protein 1 recruits histone deacetylase 2 to the promoter region of nuclear receptor binding protein 2 to affect the tumor microenvironment and malignancy of thyroid carcinoma

The association between ephrin receptor-A1 expression and survival in patients with cancer: a meta-analysis

Erythropoietin-producing hepatocyte kinase receptor A1 facilitating the prgression of SGC-7901 cells and its transplanted tumor by increasing the expression of interleukin-6 and vascular endothelial growth factor in tumor microenvironment

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