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

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题目：《CX3CL1/fractalkine enhances prostate cancer spinal metastasis by activating the Src/FAK pathway》（译：《CX3CL1/fractalkine 激活 Src/FAK 通路促进前列腺癌脊柱转移》）
摘要：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.（译：趋化因子在癌症的发展中起着重要的作用。C-X3-C基序趋化因子配体1（CX3CL1）已被证实能促进不同类型肿瘤的转移。作者先前的研究表明，CX3CL1（也称为fractalkine）/类固醇受体辅活化子（Src）/粘着斑激酶（FAK）信号通路与脊柱转移有关。在本研究中，观察到CX3CL1/C-X3-C基序趋化因子受体1（CX3CR1）在有脊柱转移的前列腺癌组织中较原发肿瘤高表达。CX3CR1过表达可诱导细胞增殖、迁移和侵袭，抑制细胞凋亡。然而，抑制CX3CR1可减少细胞增殖、迁移和侵袭，增加细胞凋亡。此外，Src/FAK通路被CX3CL1激活，CX3CL1依赖于表皮生长因子受体（EGFR）的Tyr992残基进行磷酸化。这些激酶的抑制剂抑制CX3CL1或CX3CR1过度表达诱导的细胞迁移。此外，在体内小鼠模型中，CX3CR1的过度表达诱导前列腺癌的脊柱转移。因此，CX3CL1及其对EGFR、Src和FAK通路的调控可能是早期预防前列腺癌脊柱转移的潜在靶点。）
期刊：International Journal of Oncology
Impact Factor: 3.333
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研究作者：刘鹏
研究单位：上海中山医院骨科
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