6374

CXCL5

Prostate cancers that are resistant to hormone therapy are more invasive and have greater ability to spread to other organs than androgen-dependent prostate cancers. Furthermore, this type of prostate cancer is also highly resistant to current forms of chemotherapy. This study analyzed CXCL5/ENA78, which is highly expressed in androgen-independent prostate cancers, and is responsible for cell migration and epithelial-to-mesenchymal transition in two androgen-independent prostate cancer cell lines. Inducement of PC-3 and DU145 cancer progression by CXCL5/ENA78 is associated with increased Raf/MEK/ERK activation, and the upregulation of early growth response-1 (Egr-1) and Snail. Blockade of Egr-1 decreased Snail upregulation and cell migration, indicating that Egr-1 is required in CXCL5/ENA78-mediated Snail enhancement and cell migration. In addition, Egr-1 siRNA also decreased the effect of CXCL5/ENA78 on p27 inhibition, Cdk4 induction and cell proliferation, suggesting Egr-1 is also involved in CXCL5/ENA78-mediated cell growth. Moreover, blocking ERK1/2 by siRNA suppressed CXCL5/ENA78-induced Egr-1 enhancement, cell migration, and proliferation. Our study suggests that inhibition of CXCL5/ENA78-mediated ERK/Egr-1/Snail signaling is an attractive therapeutic target for androgen-independent prostate cancer.CI - Copyright (c) 2010 Wiley-Liss, Inc.

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-3beta/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-3beta/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-3beta/Snail signaling, and it may serve as a potential therapeutic target.CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.

The emergence of chemoresistance greatly increases the recurrence risk for non-muscle invasive bladder cancer (NMIBC) patients, which is still a big concern of clinicians. Understanding the mechanisms of drug resistance is of great significance for preventing and reversing it. We showed here that CXC motif chemokine ligand 5 (CXCL5) was overexpressed in mitomycin C-resistant bladder cancer cell line M-RT4. Meanwhile, parental RT4 cell treated with recombinant human CXCL5 (rhCXCL5) reduced its sensitivity to mitomycin C. Conversely, knockdown CXCL5 sensitized M-RT4 cell. We further investigated the molecular mechanisms finding that epithelial mesenchymal transition (EMT) and NF-kappaB pathway were activated in M-RT4 cell, which could be attenuated by knockdown CXCL5. All these data indicated that CXCL5 may promote mitomycin resistance by activating EMT and NF-kappaB pathway. Thus, our study identifies CXCL5 as a novel chemoresistance-related marker in NMIBC, thereby providing new strategies to overcome chemoresistance for NMIBC patients.CI - Copyright (c) 2018 Elsevier Inc. All rights reserved.