Extracellular matrix protein 1 regulates cell proliferation and trastuzumab resistance through activation of epidermal growth factor signaling.
Extracellular matrix protein 1 regulates cell proliferation and trastuzumab resistance through activation of epidermal growth factor signaling.
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DOI：
10.1186/s13058-014-0479-6
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发表时间：
2014-12-11
期刊：
影响因子：
--
通讯作者：
Shin I
中科院分区：
文献类型：
--
作者：
Lee KM;Nam K;Oh S;Lim J;Kim YP;Lee JW;Yu JH;Ahn SH;Kim SB;Noh DY;Lee T;Shin I
细胞外基质蛋白1（ECM 1）是一种分泌型糖蛋白，在细胞增殖、血管生成和分化中发挥重要作用。ECM 1在多种类型的肿瘤中的表达表明它可能促进肿瘤的发展。在这项研究中，我们研究了ECM 1在乳腺癌致癌细胞信号传导中的作用，以及其作用的潜在机制。为了研究ECM 1的功能，我们使用了重组人ECM 1和稳定调节ECM 1表达水平的病毒转导系统。我们在体外和体内研究了ECM 1对细胞增殖和细胞信号传导的影响。此外，还使用乳腺癌患者的组织和血清来确认ECM 1的效果。ECM 1蛋白在曲妥珠单抗耐药（TR）细胞中增加，与曲妥珠单抗耐药和细胞增殖相关。通过与表皮生长因子受体（EGFR）的物理相互作用，ECM 1增强了EGF处理后EGFR和细胞外信号调节激酶的磷酸化。此外，ECM 1通过上调基质金属蛋白酶9诱导的半乳糖凝集素-3切割不仅改善了粘蛋白1的表达，而且增加了EGFR和人表皮生长因子受体3蛋白的稳定性作为次级信号。ECM 1通过激活EGFR信号在乳腺癌的癌症发展和曲妥珠单抗耐药中起重要作用。本文的在线版本（doi：10.1186/s13058-014-0479-6）包含补充材料，可供授权用户使用。
Extracellular matrix protein 1 (ECM1) is a secreted glycoprotein with putative functions in cell proliferation, angiogenesis and differentiation. Expression of ECM1 in several types of carcinoma suggests that it may promote tumor development. In this study, we investigated the role of ECM1 in oncogenic cell signaling in breast cancer, and potential mechanisms for its effects. In order to find out the functional role of ECM1, we used the recombinant human ECM1 and viral transduction systems which stably regulated the expression level of ECM1. We examined the effect of ECM1 on cell proliferation and cell signaling in vitro and in vivo. Moreover, tissues and sera of patients with breast cancer were used to confirm the effect of ECM1. ECM1 protein was increased in trastuzumab-resistant (TR) cells, in association with trastuzumab resistance and cell proliferation. Through physical interaction with epidermal growth factor receptor (EGFR), ECM1 potentiated the phosphorylation of EGFR and extracellular signal-regulated kinase upon EGF treatment. Moreover, ECM1-induced galectin-3 cleavage through upregulation of matrix metalloproteinase 9 not only improved mucin 1 expression, but also increased EGFR and human epidermal growth factor receptor 3 protein stability as a secondary signaling. ECM1 has important roles in both cancer development and trastuzumab resistance in breast cancer through activation of EGFR signaling. The online version of this article (doi:10.1186/s13058-014-0479-6) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.89.10.4285
发表时间：
1992-05-15
影响因子：
11.1
作者：
CARTER, P;PRESTA, L;SHEPARD, HM
通讯作者：
SHEPARD, HM
影响因子：
3.2
作者：
Goldenberg, MM
通讯作者：
Goldenberg, MM
影响因子：
8
作者：
Merlin, J.;Stechly, L.;Pigny, P.
通讯作者：
Pigny, P.
影响因子：
4.8
作者：
Cascio, Sandra;Zhang, Lixin;Finn, Olivera J.
通讯作者：
Finn, Olivera J.
ECM1 通过 S1P1 的重新表达控制 Th2 细胞从淋巴结的流出
影响因子：
30.5
作者：
Li, Zhenhu;Zhang, Yuan;Sun, Bing
通讯作者：
Sun, Bing