CX3CL1/fractalkine enhances prostate cancer spinal metastasis by activating the Src/FAK pathway

Liu,Peng; Liang,Yun; Jiang,Libo; Wang,Houlei; Wang,Shengxing; Dong,Jian

doi:10.3892/ijo.2018.4487

CX3CL1/fractalkine enhances prostate cancer spinal metastasis by activating the Src/FAK pathway

Authors:
- Peng Liu
- Yun Liang
- Libo Jiang
- Houlei Wang
- Shengxing Wang
- Jian Dong
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Affiliations: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: July 18, 2018 https://doi.org/10.3892/ijo.2018.4487
Pages: 1544-1556
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemokines serve important roles in the development of cancer. C-X3-C motif chemokine ligand 1 (CX3CL1) has been demonstrated to promote metastases in different types of tumors. The authors' previous studies demonstrated that the CX3CL1 (also termed fractalkine)/steroid receptor coactivator (Src)/focal adhesion kinase (FAK) signaling pathway is associated with spinal metastasis. In the present study, it was observed that CX3CL1/C-X3-C motif chemokine receptor 1 (CX3CR1) was overexpressed in prostate cancer tissues with spinal metastasis compared with primary tumors. Overexpression of CX3CR1 induced cell proliferation, migration and invasion, and inhibited cellular apoptosis. However, repression of CX3CR1 reduced cell proliferation, migration and invasion, and increased cellular apoptosis. In addition, the Src/FAK pathway was activated by CX3CL1, which depends on the Tyr992 residue of epidermal growth factor receptor (EGFR) for phosphorylation. The inhibitors of these kinases repressed the cell migration induced by CX3CL1 or CX3CR1 overexpression. Furthermore, overexpression of CX3CR1 induced the spinal metastasis of prostate cancer in an in vivo mouse model. Therefore, CX3CL1 and its regulation of the EGFR, Src and FAK pathways may be potential targets for the early prevention of spinal metastasis in prostate cancer.

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