RCP induces FAK phosphorylation and ovarian cancer cell invasion with inhibition by curcumin.
RCP induces FAK phosphorylation and ovarian cancer cell invasion with inhibition by curcumin.
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DOI：
10.1038/s12276-018-0078-1
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发表时间：
2018-04-27
影响因子：
12.8
通讯作者：
Lee HY
中科院分区：
文献类型：
--
作者：
Choe SR;Kim YN;Park CG;Cho KH;Cho DY;Lee HY
Rab偶联蛋白（RCP）促进癌细胞转移，并与各种癌症患者的结局有关。最近，我们发现RCP通过稳定β1整合素蛋白诱导Slug表达和癌细胞侵袭。在本研究中，我们证明FAK与RCP诱导的EGFR磷酸化和卵巢癌细胞侵袭有关，并受到姜黄素的抑制。RCP的异位表达诱导FAK磷酸化，FAK将β1整合素与EGFR连接，并与EGFR参与正调控环。有趣的是，我们首次观察到姜黄素通过阻断β1整联蛋白的稳定化从而抑制FAK和EGFR活化来减弱RCP诱导的卵巢癌细胞侵袭，为卵巢癌提供了潜在的生物标志物和这种致命疾病的治疗方法。Rab偶联蛋白（RCP）诱导的肿瘤细胞迁移与肿瘤病理生理学和患者结局有关。韩国大田市康阳大学的Hoi Young Lee及其同事先前已经证明RCP通过稳定细胞粘附受体来促进卵巢癌细胞的侵袭力。在他们的最新研究中，他们发现RCP还增加了其两种蛋白质结合伴侣的水平，并激活了生长因子信号传导的重要介质-粘着斑激酶（FAK）。有趣的是，用姜黄素（一种从香料姜黄中提取的天然化合物）治疗卵巢癌细胞，不仅阻断了RCP对细胞粘附和FAK激活的影响，还增强了化疗药物阿霉素对细胞侵袭的抑制作用。进一步的研究将确定姜黄素是否可以用来阻止卵巢癌的进展。
Rab coupling protein (RCP) aggravates cancer cell metastasis and has been implicated in various cancer patient outcomes. Recently, we showed that RCP induces Slug expression and cancer cell invasion by stabilizing the β1 integrin protein. In the present study, we demonstrated that FAK is implicated in RCP-induced EGFR phosphorylation and ovarian cancer cell invasion with inhibition by curcumin. Ectopic expression of RCP induced FAK phosphorylation, which links β1 integrin with EGFR and participates in a positive regulation loop with EGFR. Interestingly, we observed for the first time that curcumin attenuates RCP-induced ovarian cancer cell invasion by blocking stabilization of β1 integrin and consequently inhibiting FAK and EGFR activation, providing potential biomarkers for ovarian cancer and therapeutic approaches for this deadly disease. Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. Hoi Young Lee and colleagues at Konyang University in Daejeon, South Korea, have previously shown that RCP promotes ovarian cancer cell invasiveness by stabilizing cell adhesion receptors. In their latest study they find that RCP also increases the levels of two of its protein-binding partners and activates an important mediator of growth factor signaling, Focal Adhesion Kinase (FAK). Interestingly, treating ovarian cancer cells with curcumin, a natural compound extracted from the spice turmeric, not only blocked the effects of RCP on cell adhesion and FAK activation, it also potentiated the inhibitory effects of the chemotherapeutic agent doxorubicin on cell invasiveness. Further research will determine whether curcumin could be used to halt ovarian cancer progression.
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DOI：
10.1155/2013/541695
发表时间：
2013
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Chen CC;Sureshbabul M;Chen HW;Lin YS;Lee JY;Hong QS;Yang YC;Yu SL
通讯作者：
Yu SL
影响因子：
4.7
作者：
Chen, Chi-Hau;Shyu, Ming-Kwang;Huang, Min-Chuan
通讯作者：
Huang, Min-Chuan
影响因子：
4.8
作者：
Lindsay, AJ;Hendrick, AG;McCaffrey, MW
通讯作者：
McCaffrey, MW
影响因子：
7.5
作者：
Mukherjee S;Mazumdar M;Chakraborty S;Manna A;Saha S;Khan P;Bhattacharjee P;Guha D;Adhikary A;Mukhjerjee S;Das T
通讯作者：
Das T
影响因子：
21.3
作者：
Nader, Guilherme P. F.;Ezratty, Ellen J.;Gundersen, Gregg G.
通讯作者：
Gundersen, Gregg G.