CXCR4 is a prognostic marker that inhibits the invasion and migration of gastric cancer by regulating VEGF expression

Abstract

Metastasis is the main cause of poor prognosis of patients with gastric cancer (GC). Thus, current research is focused on identifying biomarkers that can predict the prognosis of patients with GC. C-X-C motif chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) have been reported to play important roles in different types of malignancies; however, their role in the prognosis of GC remains unknown. The present study aimed to investigate the potential role of CXCR4 and VEGF in predicting the prognosis of patients with GC. Immunohistochemistry analysis was performed to analyze the expression levels of CXCR4 and VEGF in a GC tissue microarray containing GC tissues and adjacent normal tissues. The association between CXCR4 or VEGF expression levels and the clinicopathological characteristics or survival outcomes were assessed. Furthermore, Transwell and wound healing assays were performed to determine the cell invasive and migratory abilities in vitro . The results demonstrated that CXCR4 promoted AGS cell invasion and migration by regulating VEGF expression. In addition, CXCR4 and VEGF expression levels were significantly upregulated in GC tissues compared with adjacent normal tissues, which was associated with a poorer overall survival (OS). Cox regression analysis demonstrated that both upregulated CXCR4 and VEGF expression were independent negative biomarkers of OS. To the best of our knowledge, the present study was the first to discover that CXCR4 and VEGF exert synergistic roles as efficient prognostic indicators for patients with GC.

KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression

“…Previous studies have shown that gastric cancer patients with high expression of CXCR4 have a poor prognosis and therefore, CXCR4 can be used as a prognostic marker of gastric cancer [36,37]. CXCR4 is a stem cell marker of GC cells and promote their proliferation and metastasis [36][37][38][39][40][41]. Further studies showed that the knockdown or addition of the KDM6B enzyme activity inhibitor, GSK-J4, can downregulate the expression of CXCR4 in gastric cancer cells.…”

“…Finally, we selected CXCR4 as a downstream target gene of KDM6B. Previous studies have shown that gastric cancer patients with high expression of CXCR4 have a poor prognosis and therefore, CXCR4 can be used as a prognostic marker of gastric cancer [36,37]. CXCR4 is a stem cell marker of GC cells and promote their proliferation and metastasis [36][37][38][39][40][41].…”

KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression

“…Finally, we selected CXCR4 as a downstream target gene of KDM6B. Previous studies have shown that gastric cancer patients with high expression of CXCR4 have a poor prognosis and therefore, CXCR4 can be used as a prognostic marker of gastric cancer 36,37 . CXCR4 is a stem cell marker of GC cells and promote their proliferation and metastasis [36][37][38][39][40][41] .…”

“…Previous studies have shown that gastric cancer patients with high expression of CXCR4 have a poor prognosis and therefore, CXCR4 can be used as a prognostic marker of gastric cancer 36,37 . CXCR4 is a stem cell marker of GC cells and promote their proliferation and metastasis [36][37][38][39][40][41] . Further studies showed that the knockdown or addition of the KDM6B enzyme activity inhibitor, GSK-J4, can downregulate the expression of CXCR4 in gastric cancer cells.…”

Explorando a quinase aurora A como alvo terapêutico em células iniciadoras de tumor pulmonares induzidas por>i< KRAS>/i<

“…Além disso, o eixo CXCR4/CXCL12 regula positivamente a expressão de VEGF. A inibição de CXCR4 inibe a formação de novos vasos em camundongos imunodeficientes e reduz a migração e invasão in vitro de células oriundas de pacientes com câncer gástrico (Salvucci et al 2002;Chen et al 2021).…”