FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer.
FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer.
复制标题
载脂蛋白 E 缺失诱导的细胞/基质粘附中的 FAK-ERK 激活会刺激卵巢癌的恶性进展。
DOI：
10.1186/s13046-018-0696-4
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发表时间：
2018-02-20
期刊：
影响因子：
--
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Lai H;Zhao X;Qin Y;Ding Y;Chen R;Li G;Labrie M;Ding Z;Zhou J;Hu J;Ma D;Fang Y;Gao Q
细胞外基质（ECM）是肿瘤进展的介质。然而，肿瘤形成前腹膜内 ECM 的改变是否影响卵巢癌的恶性进展仍不清楚。使用载脂蛋白 (ApoE) 敲除小鼠通过量化 ECM 主要成分来分析腹膜内 ECM 的变化。 ID8细胞被植入体内以产生同种异体移植物，并在体外对人卵巢癌细胞系进行表征，以评估ECM改变对卵巢癌恶性进展的影响。采用粘附测定、免疫化学、细胞因子谱、增殖测定、Transwell侵袭测定和蛋白质印迹来确定卵巢癌细胞的恶性表型。 ApoE 损失导致 ECM 沉积增加，从而刺激卵巢癌细胞的粘附。粘附介导的粘着斑激酶 (FAK) 信号通过激活 ERK-MMP 连接增强卵巢癌细胞的侵袭行为。这种 ECM 诱导的信号级联在体外人卵巢癌细胞系中得到进一步证实。此外，发现用 BAPN 逆转 ECM 积累或用 MEK 抑制剂 (MEKi) 消除卵巢癌细胞中粘附诱导的 ERK 激活，可有效延缓卵巢癌进展。这些发现确定了卵巢癌恶性进展中细胞/基质粘附中FAK-ERK的激活以及BAPN或MEKi抑制肿瘤的效率，为进一步研究探索新的抗癌治疗组合的可能性提供了动力。本文的在线版本 (10.1186/s13046-018-0696-4) 包含补充材料，可供授权用户使用。
Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remains elusive. Apolipoprotein (ApoE) knock-out mice was used to analyze the intraperitoneal ECM alterations by quantification of the major components of ECM. ID8 cells were implanted in vivo to generate allografts and human ovarian cancer cell lines were characterized in vitro to assess the effects of ECM alterations on the malignant progression of ovarian cancer. Adhesion assay, immunochemistry, cytokines profile, proliferation assay, transwell invasion assay and western blot were used to determine the malignant phenotype of ovarian cancer cells. ApoE loss induced increased ECM deposition, which stimulated the adhesions of ovarian cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling enhanced the invasive behaviors of ovarian cancer cells through activation of a ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in human ovarian cancer cell lines in vitro. Furthermore, reversal of the ECM accumulation with BAPN or abrogation of adhesion-induced ERK activation in ovarian cancer cells with MEK inhibitors (MEKi) was found to effectively delay ovarian cancer progression. These findings identify the FAK-ERK activation in cell/matrix adhesion in the malignant progression of ovarian cancer and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus for further studies to explore the possibility of new anticancer therapeutic combinations. The online version of this article (10.1186/s13046-018-0696-4) contains supplementary material, which is available to authorized users.
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影响因子：
8
作者：
Fang D;Chen H;Zhu JY;Wang W;Teng Y;Ding HF;Jing Q;Su SB;Huang S
通讯作者：
Huang S
影响因子：
3.7
作者：
Bondareva A;Downey CM;Ayres F;Liu W;Boyd SK;Hallgrimsson B;Jirik FR
通讯作者：
Jirik FR
影响因子：
4.3
作者：
Cox TR;Erler JT
通讯作者：
Erler JT
DOI：
10.1016/j.nhtm.2016.03.001
发表时间：
2016-01
期刊：
New horizons in translational medicine
影响因子：
--
作者：
Bhome R;Al Saihati HA;Goh RW;Bullock MD;Primrose JN;Thomas GJ;Sayan AE;Mirnezami AH
通讯作者：
Mirnezami AH
影响因子：
28.2
作者：
DeFilippis RA;Chang H;Dumont N;Rabban JT;Chen YY;Fontenay GV;Berman HK;Gauthier ML;Zhao J;Hu D;Marx JJ;Tjoe JA;Ziv E;Febbraio M;Kerlikowske K;Parvin B;Tlsty TD
通讯作者：
Tlsty TD