Fractalkine/CX3CR1 axis modulated the development of pancreatic ductal adenocarcinoma via JAK/STAT signaling pathway
Fractalkine/CX3CR1 axis modulated the development of pancreatic ductal adenocarcinoma via JAK/STAT signaling pathway
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Fractalkine/CX3CR1轴通过JAK/STAT信号通路调节胰腺导管腺癌的发生
DOI：
10.1016/j.bbrc.2017.10.006
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发表时间：
2017-12-02
影响因子：
3.1
通讯作者：
Wang, Feng
中科院分区：
文献类型：
--
作者：
Huang, LiYa;Ma, BinWu;Wang, Feng
胰腺导管腺癌(PDAC)是一种致命的恶性肿瘤，估计5年生存率约占所有分期总和的5%。PDAC的高转移潜能是导致高死亡率和不良预后的主要原因。大多数患者在确诊时存在远处转移。Fractalkine(FKN)是一种趋化因子，是CX3CR1的特异性配体。已有报道FKN/CX3CR1系统在多种实体瘤中表达上调。然而，FKN/CX3CR1在PDAC发生发展中的作用尚不清楚。在目前的研究中，我们发现FKN和CX3CR1在PDAC组织中的表达显著增加，尤其是在转移的标本中，并且与PDAC的严重程度密切相关。FKN的异位表达促进了PDAC的增殖和迁移，而CX3CR1的敲除则逆转了FKN的功能。此外，FKN缺乏的PDAC细胞表现出增殖和迁移活性受损。其潜在机制是FKN/CX3CR1激活JAK/STAT信号，进而调节细胞生长。体内成瘤实验一致地证实了FKN/CX3CR1在PDAC生长中的调节作用。我们的研究有助于了解PDAC的发生机制，并证实了FKN/CX3CR1在PDAC发生发展中的关键作用。(C)2017 Elsevier Inc.保留所有权利。
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an estimated 5 year survival rate of approximately 5% of all stages combined. High potential of PDAC metastasis is a leading cause for high mortality and poor prognosis. The majority of patients present with distant metastasis at diagnosis. Fractalkine (FKN) is recognized as a chemokine and a specific ligand of CX3CR1. It has been reported that FKN/CX3CR1 system was upregulated in many types of solid tumors. However, role of FKN/CX3CR1 in PDAC development remains unclear. In the current investigation, we found that FKN and CX3CR1 expression was significantly increased in PDAC tissues, especially in the metastatic samples, and was highly-correlated with severity of PDAC. Ectopic expression of FKN promoted the proliferation and migration of PDAC, while knockdown of CX3CR1 reversed the function of FKN. In addition, PDAC cells with FKN-deficiency showed impaired proliferation and migration activity. The underlying mechanism is that FKN/CX3CR1 activated JAK/STAT signaling, which in turn regulated cell growth. Consistently, in vivo tumorigenesis assay validated the regulatory role of FKN/CX3CR1 in PDAC growth. Our investigation helped understanding the pathogenesis of PDAC occurrence, and demonstrated critical role of FKN/CX3CR1 in PDAC development. (C) 2017 Elsevier Inc. All rights reserved.