CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

Qi, Xin; Zhang, Na; Yu, Haibo; Zhang, Qin; Cui, Yanfen; Zhang, Chuanshan; Ma, Zhe; Yang, Yan; Liu, Wei

doi:10.3748/wjg.v23.i17.3053

Cited by 24 publications

(15 citation statements)

References 38 publications

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“…Among 27 studies, three studies each evaluated colorectal carcinoma (or rectal cancer) 18 - 20 , hepatocellular carcinoma 21 - 23 , esophageal carcinoma (or esophageal squamous cell carcinoma) 13 , 24 , 25 , and thyroid carcinoma 26 - 28 . Two studies evaluated renal cell carcinoma 29 , 30 , pancreatic cancer 31 , 32 , cervical cancer (or cervical squamous cell carcinoma) 33 , 34 , nasopharyngeal carcinoma 35 , 36 , glioma or glioblastoma 37 , 38 and gastric cancer 39 , 40 . One study evaluated gallbladder cancer 14 , cutaneous squamous cell carcinoma 41 and chondrosarcoma 42 .…”

Section: Meta-analysis Resultsmentioning

confidence: 99%

Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Zhao¹,

Zhang²,

Qin³

et al. 2018

J. Cancer

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Background: Accumulating evidence indicated that the CXC chemokine receptor (CXCR) 7 (CXCR7) was overexpressed in a variety of tumors. However, the value of the CXCR7 expression in predicting prognosis in solid tumors remains controversial. Therefore, we performed this meta-analysis to evaluate the correlation between CXCR7 expression and lymph node metastasis (LNM), tumor pathological grade and survival, including overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS).Methods: Eligible studies were searched in PubMed, Web of Science, and PMC up to April 2018. A total of 27 studies were included in this meta-analysis. Odds ratio (OR), hazard ratio (HR) and 95 % confidence intervals (CI) were used as effect measures.Results: The meta-analysis showed that high expression of CXCR7 predicted a high risk of LNM (pooled OR = 2.22, 95%CI: 1.41-3.50), high tumor grade (pooled OR = 1.94, 95%CI: 1.20-3.13), poor OS (pooled HR = 1.66, 95%CI: 1.30-2.03), and poor DFS/RFS (pooled HR = 1.82, 95%CI: 1.21-2.43). Subgroup analysis showed that CXCR7 expression had a positive correlation with LNM in pan-adenocarcinoma subgroup (pooled OR = 3.73, 95%CI: 2.21-6.30), while no correlation was found in pan-squamous cancer subgroup (pooled OR = 1.29, 95%CI: 0.56-2.96). Subgroup analysis of tumor grade revealed that high expression of CXCR7 predicted high tumor grade both in pan-squamous cancer and pan-adenocarcinoma (pooled OR = 3.58, 95%CI: 1.39-9.22, pooled OR = 2.25, 95%CI: 1.20-4.20). As in OS group, we divided the data based on analysis method and it turned out that overexpressed CXCR7 predicted worse OS both in multivariate analysis (pooled HR =1.57, 95%CI: 1.12-2.01) and univariate analysis subgroup (pooled HR =1.86, 95%CI: 1.23-2.49).Conclusions: Our meta-analysis revealed that high expression of CXCR7 predicted unfavorable prognosis and may serve as potential targets of cancer therapy.

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Section: Meta-analysis Resultsmentioning

confidence: 99%

Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Zhao¹,

Zhang²,

Qin³

et al. 2018

J. Cancer

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“…CXCR7, also known as RDC1, is one of the CXCR subtype cytokines. The activation of CXCR7 by its ligand CXCL12 could promote cell migration, angiogenesis, tumorigenesis, invasion, metastasis and anti-apoptosis [25]. CXCR7 is considered to be an EMT-related gene and is highly expressed in various cancer cells [26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

SOX4 promotes the growth and metastasis of breast cancer

et al. 2020

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Purpose Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo. Methods We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging. Results SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel. Conclusions SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

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“…The NAGLU gene was found to be low‐methylated and in negative correlation to HCC stage by comparing T2D with ND and HCC with the control group (Figure d–f). It was shown that processing of CXCL12 impedes the recruitment of endothelial progenitor cells in diabetic wound healing (Feng et al, ), CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma (Xin et al, ). DDX5 and KL genes were found to be low‐methylated and in positive correlation with HCC stage by comparing T2D with ND and HCC with the control group (Figure g,h).…”

Section: Resultsmentioning

confidence: 99%

The underlying pathophysiology association between the Type 2‐diabetic and hepatocellular carcinoma

Wei

Wang

et al. 2018

Journal Cellular Physiology

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Type 2‐diabetic (T2D) disease has been reported to increase the incidence of liver cancer, however, the underlying pathophysiology is still not fully understood. Here, we aimed to reveal the underlying pathophysiology association between the T2D and hepatocellular carcinoma (HCC) and, therefore, to find the possible therapeutic targets in the occurrence and development of HCC. The methylation microarray data of T2D and HCC were extracted from the Gene Expression Omnibus and The Cancer Genome Atlas. A total of 504 differentially methylated genes (DMGs) between T2D samples and the controls were identified, whereas 6269 DMGs were identified between HCC samples and the control groups. There were 336 DMGs coexisting in diabetes and HCC, among which 86 genes were comethylated genes. These genes were mostly enriched in pathways as glycosaminoglycan biosynthesis, fatty acid, and metabolic pathway as glycosaminoglycan degradation and thiamine, fructose and mannose. There were 250 DMGs that had differential methylation direction between T2D DMGs and HCC DMGs, and these genes were enriched in the Sphingolipid metabolism pathway and immune pathways through natural killer cell‐mediated cytotoxicity and ak‐STAT signaling pathway. Eight genes were found related to the occurrence and development of diabetes and HCC. Moreover, the result of protein‐protein interaction network showed that CDKN1A gene was related to the prognosis of HCC. In summary, eight genes were found to be associated with the development of HCC and CDKN1A may serve as the potential prognostic gene for HCC.

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CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

Cited by 24 publications

References 38 publications

Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

SOX4 promotes the growth and metastasis of breast cancer

The underlying pathophysiology association between the Type 2‐diabetic and hepatocellular carcinoma

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