The synergistic effects of CXCR4 and EGFR on promoting EGF-mediated metastasis in ovarian cancer cells
The synergistic effects of CXCR4 and EGFR on promoting EGF-mediated metastasis in ovarian cancer cells
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DOI：
10.1016/j.colsurfb.2007.05.013
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发表时间：
2007-10-15
影响因子：
5.8
通讯作者：
Liu, Yiyao
中科院分区：
文献类型：
--
作者：
Guo, Zhigang;Cai, Shaoxi;Liu, Yiyao
CXC趋化因子受体4(CXCR4)是一种细胞表面受体，已被报道介导卵巢、乳腺、肺和前列腺等多种实体肿瘤的转移。表皮生长因子受体(EGFR)的过度表达与大多数卵巢癌有关，并通过促进细胞增殖、存活和运动而参与恶性转化过程。在本研究中，首次发现表皮生长因子(EGF)促进CXCR4的表达和卵巢癌细胞的迁移，并且基质细胞衍生因子-1α(SDF-1α)和EGF诱导的高基质金属肽酶9(MMP9)的表达。分子分析表明，CXCR4和MMP9的表达增强受磷脂酰肌醇-3-激酶(PI3K)/Akt信号转导途径的调节。这些结果提示CXCR4和EGFR之间可能存在重要的细胞内通路，可能与肿瘤恶化的信号联系在一起，并为在组织切片中检测到CXCR4和EGFR共同表达的患者总体生存率较低提供了合理的解释。这说明，与单独抑制EGFR或CXCR4信号相比，同时抑制它们可能是一种更有用的癌症治疗策略。(C)2007 Elsevier B.V.保留所有权利。
CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been reported to mediate the metastasis of many solid tumors including ovarian, breast, lung and prostate. The over-expression of the epidermal growth factor receptor (EGFR) is associated with the majority of ovarian cancer and has been implicated in the process of malignant transformation by promoting cell proliferation, survival, and motility. In this research, the result first showed that epidermis growth factor (EGF) enhanced the expression of CXCR4 and the migration of ovarian cancer cells, moreover, both stromal cell derived factor-1 alpha (SDF-1 alpha) and EGF-induced high matrix metallopepticlase 9 (MMP9) expressions. Molecular analysis indicated that augmented CXCR4 and MMP9 expression was regulated by phosphatidylinositol-3-kinase(PI3K)/Akt signal transduction pathway. These results suggested a possible important "cross-talk" between CXCR4 and EGFR intracellular pathways that might link signals of tumor deteriorated and provided a plausible explanation for the poor overall survival rate of patients whose co-expression of CXCR4 and EGFR was detected in their tissue sections. It enlightened that, compared to the respective inhibition of the EGFR or CXCR4 signaling, the simultaneous inhibition of them might be a more useful therapeutic strategy of cancer. (c) 2007 Elsevier B.V. All rights reserved.