Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through modulating YAP1-FAK/PXN signaling.
Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through modulating YAP1-FAK/PXN signaling.
复制标题
细胞质LIF重新编程可通过调节YAP1-FAK/PXN信号传导来增强NPC传播。
DOI：
10.1038/s41467-018-07660-6
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发表时间：
2018-11-30
影响因子：
16.6
通讯作者：
Tsang NM
中科院分区：
文献类型：
--
作者：
Liu SC;Hsu T;Chang YS;Chung AK;Jiang SS;OuYang CN;Yuh CH;Hsueh C;Liu YP;Tsang NM
转移仍然是鼻咽癌临床上未解决的问题。在这里，我们报告说，较高水平的细胞质白血病抑制因子（LIF）和LIF受体与较差的转移/无复发生存。此外，在NPC中鉴定了LIF的单核苷酸变异和信号肽突变。胞质LIF通过获得EMT和侵袭足相关特征将侵袭模式从集体迁移重新编程为间质迁移。较高的胞质LIF通过调节YAP 1-FAK/PXN信号传导机制增强癌血管播散和局部侵袭。免疫组化分析显示，鼻咽癌活检细胞质LIF表达与黏着斑激酶呈正相关。AZD 0530的药物干预通过促进YAP 1的细胞质积累和抑制粘着斑激酶，显著逆转LIF介导的癌症扩散和局部侵袭。鉴于LIF/YAP 1-粘着斑信号在癌症传播中的重要作用，靶向该途径提供了阻断转移的有希望的机会。调控鼻咽癌转移的分子途径尚不清楚。在这里，他们报告了较高水平的细胞质白血病抑制因子（cLIF）和LIF受体（LIFR）与NPC患者的较高转移相关，并显示cLIF通过YAP 1-FAK/PXN轴促进NPC转移和血管播散。
Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis. Molecular pathways regulating nasopharyngeal carcinoma (NPC) metastasis are unclear. Here they report higher levels of cytoplasmic leukemia inhibitory factor (cLIF) and LIF receptor (LIFR) to correlate with higher metastasis in NPC patients, and show cLIF to promote NPC metastasis and vascular dissemination via the YAP1-FAK/PXN axis.
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DOI：
10.1186/1476-5926-3-10
发表时间：
2004-11-26
期刊：
Comparative hepatology
影响因子：
--
作者：
Hisaka, Toru;Desmouliere, Alexis;Rosenbaum, Jean
通讯作者：
Rosenbaum, Jean
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.8
作者：
Dimitriadis, E.;Menkhorst, E.;Paiva, P.
通讯作者：
Paiva, P.
影响因子：
4.4
作者：
Anhuf, D;Weissenbach, M;Schaper, F
通讯作者：
Schaper, F
影响因子：
7.5
作者：
Gimona, Mario;Buccione, Roberto;Linder, Stefan
通讯作者：
Linder, Stefan