CX3CL1 increases invasiveness and metastasis by promoting epithelial-to-mesenchymal transition through the TACE/TGF-α/EGFR pathway in hypoxic androgen‑independent prostate cancer cells.

Epithelial-to-mesenchymal transition (EMT) endows cancer cells with enhanced invasive and metastatic potential during cancer progression. Fractalkine, also known as chemokine (C-X3-C motif) ligand 1 (CX3CL1), the only member recognized so far that belongs to the CX3C chemokine subfamily, was reported to participate in the molecular events that regulate cell adhesion, migration and survival of human prostate cancer cells.

However, the relationship between CX3CL1 and EMT remains unknown. We treated DU145 and PC-3 cells with CX3CL1 under hypoxic conditions. The migration and invasion abilities of DU145 and PC-3 cells were detected by Transwell assays. Induction of EMT was verified by morphological changes in the DU145 and PC-3 cells and analysis of protein expression of EMT markers such as E-cadherin and vimentin. To identify the involved signaling pathway in CX3CL1-induced EMT, activation of epidermal growth factor receptor (EGFR) was measured using western blot analysis, and Slug expression was detected with or without an EGFR inhibitor prior to CX3CL1 treatment. Concentrations of soluble and total TGF-α in the CX3CL‑treated DU145 cells were detected by ELISA. Additionally, we determined the involvement of the TACE/TGF-α/EGFR pathway in CX3CL1‑induced EMT using RNA interference and specific inhibitors. CX3CL1 increased the migration and invasiveness of the DU145 and PC-3 cells, and resulted in characteristic alterations of EMT. Our results demonstrated that TACE/TGF-α/EGFR pathway activation and subsequent upregulation of Slug expression were responsible for CX3CL1‑induced EMT, and contributed to the migration and inva-sion of prostate cancer cells. Inhibition of TACE/TGF-α/EGFR signaling reversed EMT and led to reduced migration and invasion abilities of the prostate cancer cells. We provide initial evidence that CX3CL1 exposure resulted in EMT occurrence and enhancement of cell migration and invasion through a mechanism involving activation of TACE/TGF-α/EGFR signaling. These findings revealed that CX3CL1 may serve as a new target for the treatment of prostate cancer.

Oncology reports. 2015 Dec 02 [Epub]

Jiebing Tang, Lijie Xiao, Rongjun Cui, Dong Li, Xiulan Zheng, Lijuan Zhu, Hui Sun, Yujia Pan, Yandan Du, Xiaoguang Yu

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Ultrasonography, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. , Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.

PubMed

E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe