The Experts below are selected from a list of 4431 Experts worldwide ranked by ideXlab platform
Jian Zhou - One of the best experts on this subject based on the ideXlab platform.
-
neutrophil infiltration mediated by CXCL5 accumulation in the laryngeal squamous cell carcinoma microenvironment a mechanism by which tumour cells escape immune surveillance
Clinical Immunology, 2017Co-Authors: Duo Zhang, Jian Zhou, Di Tang, Lin Zhou, Liang Chou, Kuangyen Chou, Liming LuAbstract:Abstract The CXCL5 chemokine is important for neutrophil accumulation in tumour tissues. In this report, we attempted to clarify whether and how infiltrating tumour-associated neutrophils (TANs) in laryngeal squamous cell carcinoma (LSCC) affect the proliferation and activation of T cells. We examined chemokine expression by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and performed an immunohistochemical analysis of LSCC microarrays. The relationship between CXCL5 and CD66b (a neutrophil marker) was investigated by immunofluorescence staining. We found that CXCL5 was upregulated in LSCC tissues, whereas CXCL5 levels were decreased in LSCC patient serum. Furthermore, high levels of CXCL5 were significantly correlated with intratumoural neutrophil infiltration. Compared with peripheral blood neutrophils (PBNs), TANs significantly inhibited T cell proliferation and decreased IFN-γ and TNF-α secretion. These data suggest that excessive neutrophil infiltration is associated with advanced clinical stages of LSCC (T3 or T4, III or IV, and N1 or N2).
-
cxcr2 CXCL5 axis contributes to epithelial mesenchymal transition of hcc cells through activating pi3k akt gsk 3β snail signaling
Cancer Letters, 2015Co-Authors: Shaolai Zhou, Zhengjun Zhou, Zheng Wang, Xiaowu Huang, Zhi-qiang Hu, Xun Li, Jian ZhouAbstract:Abstract Upregulation of CXCR2 in tumor cells has been documented in several types of cancer. As one of its ligands, CXCL5 is associated with neutrophil infiltration and poor prognosis in hepatocellular carcinoma (HCC). However, little is known about the role of the CXCR2/CXCL5 axis in the invasion and metastasis of HCC cells. In this study, we examined CXCR2 expression in human HCC cell lines and in three independent cohorts of HCC patients. The molecular effects of high expression levels of CXCR2 and CXCL5 in HCC cells were determined using qRT-PCR, western blot analysis, immunofluorescence, matrigel invasion assay, and xenograft mouse models. We found that high levels of CXCR2 correlated with progression and poor prognosis in human HCC. CXCR2/CXCL5 together promoted cell spreading by inducing the epithelial–mesenchymal transition (EMT) through activation of the PI3K/Akt/GSK-3β/Snail signaling pathway. In clinical HCC samples, high expression of both CXCR2 and CXCL5 showed a significant correlation with the activation of PI3K/Akt/GSK-3β/Snail signaling and EMT phenotype. In conclusion, our data showed that the CXCR2/CXCL5 axis contributes to EMT of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling, and it may serve as a potential therapeutic target.
-
CXCR2/CXCL5 axis contributes to epithelial–mesenchymal transition of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling
Cancer Letters, 2014Co-Authors: Shaolai Zhou, Zhengjun Zhou, Zheng Wang, Xiaowu Huang, Zhi-qiang Hu, Xun Li, Jian ZhouAbstract:Abstract Upregulation of CXCR2 in tumor cells has been documented in several types of cancer. As one of its ligands, CXCL5 is associated with neutrophil infiltration and poor prognosis in hepatocellular carcinoma (HCC). However, little is known about the role of the CXCR2/CXCL5 axis in the invasion and metastasis of HCC cells. In this study, we examined CXCR2 expression in human HCC cell lines and in three independent cohorts of HCC patients. The molecular effects of high expression levels of CXCR2 and CXCL5 in HCC cells were determined using qRT-PCR, western blot analysis, immunofluorescence, matrigel invasion assay, and xenograft mouse models. We found that high levels of CXCR2 correlated with progression and poor prognosis in human HCC. CXCR2/CXCL5 together promoted cell spreading by inducing the epithelial–mesenchymal transition (EMT) through activation of the PI3K/Akt/GSK-3β/Snail signaling pathway. In clinical HCC samples, high expression of both CXCR2 and CXCL5 showed a significant correlation with the activation of PI3K/Akt/GSK-3β/Snail signaling and EMT phenotype. In conclusion, our data showed that the CXCR2/CXCL5 axis contributes to EMT of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling, and it may serve as a potential therapeutic target.
-
overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma
Hepatology, 2012Co-Authors: Shaolai Zhou, Zhengjun Zhou, Xiaoying Wang, Guohuan Yang, Zheng Wang, Xiaowu Huang, Jian ZhouAbstract:CXCL5 (epithelial neutrophil-activating peptide-78) is a member of a proangiogenic subgroup of the CXC-type chemokine family of small, secreted proteins. Recently, evidence that CXCL5 is involved in carcinogenesis and cancer progression has emerged. To investigate the role of CXCL5 in tumor growth, invasion, and prognosis of hepatocellular carcinoma (HCC), we examined CXCL5 messenger RNA (mRNA) and protein levels in HCC cell lines with various metastatic potentials and in three independent cohorts of 919 HCC patients. We found that CXCL5 expression was increased in the highly metastatic HCC cell lines and in tumor tissues from patients with recurrent HCC compared to controls. CXCL5 activated the PI3K-Akt and ERK1/2 signaling pathways in HCC cells and promoted proliferation, migration, and invasion. Furthermore, we found that CXCL5 had a direct chemoattractant effect on neutrophils in vitro. In animal studies, the up-regulation of CXCL5 in HCC cells promoted tumor growth, lung metastasis, and intratumoral neutrophil infiltration. Conversely, down-regulation of CXCL5 in HCC cells reduced tumor growth, metastasis, and intratumoral neutrophil infiltration. Immunohistochemical analysis in HCC samples showed that overexpression of CXCL5 was well correlated with intratumoral neutrophil infiltration, shorter overall survival, and tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, was an independent prognostic indicator for overall survival and cumulative recurrence. Conclusion: CXCL5 promotes HCC cell proliferation, invasion, and intratumoral neutrophil infiltration. CXCL5 overexpression, alone or combined with intratumoral neutrophil presence, is a novel prognostic predictor, and CXCL5 is a potential therapeutic target for HCC. (HEPATOLOGY 2012;56:2242–2254)
Jingkun Zhao - One of the best experts on this subject based on the ideXlab platform.
-
CXCL5 induces tumor angiogenesis via enhancing the expression of foxd1 mediated by the akt nf κb pathway in colorectal cancer
Cell Death and Disease, 2019Co-Authors: Chun Chen, Jingkun Zhao, Baochi Ou, Yaping Zong, Minhua Zheng, Hao Feng, Zhuoqing Xu, Xiaohui Shen, Aiguo LuAbstract:The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients’ tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.
-
CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer.
Cell Death and Disease, 2019Co-Authors: Chun Chen, Jingkun Zhao, Baochi Ou, Yaping Zong, Minhua Zheng, Hao Feng, Zhuoqing Xu, Xiaohui Shen, Aiguo LuAbstract:The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients’ tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.
-
tumor derived CXCL5 promotes human colorectal cancer metastasis through activation of the erk elk 1 snail and akt gsk3β β catenin pathways
Molecular Cancer, 2017Co-Authors: Jingkun Zhao, Baochi Ou, Puxiongzhi Wang, Yaping Zong, Minhua Zheng, Hao Feng, Aiguo LuAbstract:Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.
-
Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways
Molecular Cancer, 2017Co-Authors: Jingkun Zhao, Baochi Ou, Puxiongzhi Wang, Yaping Zong, Minhua Zheng, Hao FengAbstract:Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.
Shaolai Zhou - One of the best experts on this subject based on the ideXlab platform.
-
cxcr2 CXCL5 axis contributes to epithelial mesenchymal transition of hcc cells through activating pi3k akt gsk 3β snail signaling
Cancer Letters, 2015Co-Authors: Shaolai Zhou, Zhengjun Zhou, Zheng Wang, Xiaowu Huang, Zhi-qiang Hu, Xun Li, Jian ZhouAbstract:Abstract Upregulation of CXCR2 in tumor cells has been documented in several types of cancer. As one of its ligands, CXCL5 is associated with neutrophil infiltration and poor prognosis in hepatocellular carcinoma (HCC). However, little is known about the role of the CXCR2/CXCL5 axis in the invasion and metastasis of HCC cells. In this study, we examined CXCR2 expression in human HCC cell lines and in three independent cohorts of HCC patients. The molecular effects of high expression levels of CXCR2 and CXCL5 in HCC cells were determined using qRT-PCR, western blot analysis, immunofluorescence, matrigel invasion assay, and xenograft mouse models. We found that high levels of CXCR2 correlated with progression and poor prognosis in human HCC. CXCR2/CXCL5 together promoted cell spreading by inducing the epithelial–mesenchymal transition (EMT) through activation of the PI3K/Akt/GSK-3β/Snail signaling pathway. In clinical HCC samples, high expression of both CXCR2 and CXCL5 showed a significant correlation with the activation of PI3K/Akt/GSK-3β/Snail signaling and EMT phenotype. In conclusion, our data showed that the CXCR2/CXCL5 axis contributes to EMT of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling, and it may serve as a potential therapeutic target.
-
CXCR2/CXCL5 axis contributes to epithelial–mesenchymal transition of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling
Cancer Letters, 2014Co-Authors: Shaolai Zhou, Zhengjun Zhou, Zheng Wang, Xiaowu Huang, Zhi-qiang Hu, Xun Li, Jian ZhouAbstract:Abstract Upregulation of CXCR2 in tumor cells has been documented in several types of cancer. As one of its ligands, CXCL5 is associated with neutrophil infiltration and poor prognosis in hepatocellular carcinoma (HCC). However, little is known about the role of the CXCR2/CXCL5 axis in the invasion and metastasis of HCC cells. In this study, we examined CXCR2 expression in human HCC cell lines and in three independent cohorts of HCC patients. The molecular effects of high expression levels of CXCR2 and CXCL5 in HCC cells were determined using qRT-PCR, western blot analysis, immunofluorescence, matrigel invasion assay, and xenograft mouse models. We found that high levels of CXCR2 correlated with progression and poor prognosis in human HCC. CXCR2/CXCL5 together promoted cell spreading by inducing the epithelial–mesenchymal transition (EMT) through activation of the PI3K/Akt/GSK-3β/Snail signaling pathway. In clinical HCC samples, high expression of both CXCR2 and CXCL5 showed a significant correlation with the activation of PI3K/Akt/GSK-3β/Snail signaling and EMT phenotype. In conclusion, our data showed that the CXCR2/CXCL5 axis contributes to EMT of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling, and it may serve as a potential therapeutic target.
-
CXCL5 contributes to tumor metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils.
Carcinogenesis, 2013Co-Authors: Shaolai Zhou, Zhengjun Zhou, Zheng Wang, Qing Chen, Yong-sheng Xiao, Zhi-qiang Hu, Xiao-yong Huang, Guohuan YangAbstract:CXCL5 is a member of the CXC-type chemokine family that may play a role in carcinogenesis and cancer progression. This study investigates the biological function and clinical significance of CXCL5 in intrahepatic cholangiocarcinoma (ICC). We demonstrated that CXCL5 was overexpressed in ICC cell lines and tumor samples compared with paired normal tissues. CXCL5 had a direct chemoattractant effect on neutrophils in vitro through PI3K-Akt and extracellular signal-regulated kinase 1/2 signaling pathways. In animal studies, CXCL5 promoted tumor growth and metastasis without altering in vitro proliferative and invasive ability of ICC cells, and this effect was mediated by the recruitment of intratumoral infiltrative neutrophils by tumor-derived CXCL5. Immunohistochemical analysis of ICC samples showed that overexpression of CXCL5 correlated strongly with intratumoral neutrophil infiltration, shorter overall survival and high tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, was an independent prognostic indicator for ICC. In conclusion, our data showed that CXCL5 promotes ICC growth and metastasis by recruiting intratumoral neutrophils. CXCL5 alone or combined with intratumoral neutrophils is a novel prognostic predictor for ICC patients and a potential therapeutic target.
-
overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma
Hepatology, 2012Co-Authors: Shaolai Zhou, Zhengjun Zhou, Xiaoying Wang, Guohuan Yang, Zheng Wang, Xiaowu Huang, Jian ZhouAbstract:CXCL5 (epithelial neutrophil-activating peptide-78) is a member of a proangiogenic subgroup of the CXC-type chemokine family of small, secreted proteins. Recently, evidence that CXCL5 is involved in carcinogenesis and cancer progression has emerged. To investigate the role of CXCL5 in tumor growth, invasion, and prognosis of hepatocellular carcinoma (HCC), we examined CXCL5 messenger RNA (mRNA) and protein levels in HCC cell lines with various metastatic potentials and in three independent cohorts of 919 HCC patients. We found that CXCL5 expression was increased in the highly metastatic HCC cell lines and in tumor tissues from patients with recurrent HCC compared to controls. CXCL5 activated the PI3K-Akt and ERK1/2 signaling pathways in HCC cells and promoted proliferation, migration, and invasion. Furthermore, we found that CXCL5 had a direct chemoattractant effect on neutrophils in vitro. In animal studies, the up-regulation of CXCL5 in HCC cells promoted tumor growth, lung metastasis, and intratumoral neutrophil infiltration. Conversely, down-regulation of CXCL5 in HCC cells reduced tumor growth, metastasis, and intratumoral neutrophil infiltration. Immunohistochemical analysis in HCC samples showed that overexpression of CXCL5 was well correlated with intratumoral neutrophil infiltration, shorter overall survival, and tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, was an independent prognostic indicator for overall survival and cumulative recurrence. Conclusion: CXCL5 promotes HCC cell proliferation, invasion, and intratumoral neutrophil infiltration. CXCL5 overexpression, alone or combined with intratumoral neutrophil presence, is a novel prognostic predictor, and CXCL5 is a potential therapeutic target for HCC. (HEPATOLOGY 2012;56:2242–2254)
Hai Bo Zhang - One of the best experts on this subject based on the ideXlab platform.
-
The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3β/snail signalling
Journal of Experimental & Clinical Cancer Research, 2018Co-Authors: Hai Bo Zhang, Liang Ru Ke, Jing Yang, Ya Hui Yu, Hu Liang, Xin Jun Huang, Wang Zhong LiAbstract:Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway. CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway. The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.
-
the CXCL5 cxcr2 axis contributes to the epithelial mesenchymal transition of nasopharyngeal carcinoma cells by activating erk gsk 3β snail signalling
Journal of Experimental & Clinical Cancer Research, 2018Co-Authors: Hai Bo Zhang, Yanqun Xiang, Liang Ru Ke, Jing Yang, Ya Hui Yu, Hu Liang, Xin Jun Huang, Wang Zhong Li, Tiebang Kang, Xing LvAbstract:Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway. CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway. The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.
-
a novel statistical prognostic score model that includes serum CXCL5 levels and clinical classification predicts risk of disease progression and survival of nasopharyngeal carcinoma patients
PLOS ONE, 2013Co-Authors: Hai Bo Zhang, Xing Lu, Lin Wang, Lisheng Zheng, Yanfang Ye, Yanqun XiangAbstract:Background Aberrant expression of C-X-C motif chemokine 5 (CXCL5) contributes to the progression of various cancers. This study analyzed the clinical significance of serum CXCL5 (sCXCL5) levels of nasopharyngeal carcinoma (NPC) patients, with the goal of building a novel prognostic score model. Experimental Design Serum samples were collected prior to treatment from 290 NPC patients for the detection of sCXCL5 with ELISA. Half of the patients (n = 145) were randomly assigned to the training set to generate the sCXCL5 cutoff point using receiver operator characteristic (ROC) analysis, while the other half (n = 145) were assigned to the testing set for validation. Associations between sCXCL5 levels and clinical characteristics were analyzed. A prognostic score model was built using independent predictors derived from multivariate analysis. A concordance index (C-Index) was used to evaluate prognostic ability. Results The sCXCL5 cutoff point was 0.805 ng/ml. Sex, age, histology, T classification, clinical classification and local recurrence were not associated with sCXCL5 levels. However, sCXCL5 levels were positively associated with N classification, distant metastasis and disease progression (P<0.05). A high sCXCL5 level predicted poor 6-year overall survival (OS), poor 6-year distant metastasis-free survival (DMFS), and poor 6-year progression-free survival (PFS). A prognostic score model was subsequently constructed based on sCXCL5 levels and clinical classification (C-C model), which are independent predictors of OS, DMFS, and PFS, as confirmed by the multivariate analysis. Furthermore, this novel model successfully divided the patients into four risk subgroups in the training set, the testing set and the entire set of patients. The C-Indices were 0.751 and 0.762 for the training set and the testing set, respectively. Conclusions sCXCL5 level was determined to be an independent prognostic factor for NPC patients. The novel statistical C-C model, which includes sCXCL5 levels and clinical classification, could be helpful in predicting the prognosis of NPC patients.
Aiguo Lu - One of the best experts on this subject based on the ideXlab platform.
-
CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer.
Cell Death and Disease, 2019Co-Authors: Chun Chen, Jingkun Zhao, Baochi Ou, Yaping Zong, Minhua Zheng, Hao Feng, Zhuoqing Xu, Xiaohui Shen, Aiguo LuAbstract:The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients’ tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.
-
CXCL5 induces tumor angiogenesis via enhancing the expression of foxd1 mediated by the akt nf κb pathway in colorectal cancer
Cell Death and Disease, 2019Co-Authors: Chun Chen, Jingkun Zhao, Baochi Ou, Yaping Zong, Minhua Zheng, Hao Feng, Zhuoqing Xu, Xiaohui Shen, Aiguo LuAbstract:The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients’ tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.
-
tumor derived CXCL5 promotes human colorectal cancer metastasis through activation of the erk elk 1 snail and akt gsk3β β catenin pathways
Molecular Cancer, 2017Co-Authors: Jingkun Zhao, Baochi Ou, Puxiongzhi Wang, Yaping Zong, Minhua Zheng, Hao Feng, Aiguo LuAbstract:Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.
