Stat1 and CD74 overexpression is co-dependent and linked to increased invasion and lymph node metastasis in triple-negative breast cancer
Stat1 and CD74 overexpression is co-dependent and linked to increased invasion and lymph node metastasis in triple-negative breast cancer
复制标题
DOI：
10.1016/j.jprot.2011.11.033
复制
发表时间：
2012-06-06
影响因子：
3.3
通讯作者：
Metodiev, Metodi V.
中科院分区：
文献类型：
--
作者：
Greenwood, Christina;Metodieva, Gergana;Metodiev, Metodi V.
由于缺乏合理的治疗方法，三阴性乳腺癌很难治疗。目前还没有确定的标志物和靶标可用于患者分层和靶向治疗。在这里，我们报告鉴定新的分子特征，这似乎增加转移的三阴性乳腺肿瘤。我们发现三阴性乳腺肿瘤可以根据其全基因组蛋白丰度谱分为两种表型。前者的特点是Stat1、Mx1和CD74的高表达。本组9例肿瘤中有7例浸润了至少2个淋巴结，而第二组10例肿瘤中只有1例淋巴结阳性。体外实验表明，干扰素诱导的Stat1丰度增加与培养细胞的迁移和侵袭增加有关。当CD74过表达时，它增加了细胞对基质的粘附。这种作用伴随着β -连环蛋白、MUC18、丛蛋白、整合蛋白和其他参与细胞粘附和癌症转移的蛋白的膜表达的显著增加。综上所述，我们的研究结果表明Stat1/CD74阳性三阴性肿瘤更具侵袭性，并为开发更好的三阴性乳腺癌诊断和更有针对性的治疗方法提供了一种方法。这篇文章是题为“蛋白质组学：临床联系”的特刊的一部分。(C) 2011 Elsevier B.V.版权所有
Triple-negative breast cancer is difficult to treat because of the lack of rationale-based therapies. There are no established markers and targets that can be used for stratification of patients and targeted therapy. Here we report the identification of novel molecular features, which appear to augment metastasis of triple negative breast tumors. We found that triple-negative breast tumors can be segregated into 2 phenotypes based on their genome-wide protein abundance profiles. The first is characterized by high expression of Stat1, Mx1, and CD74. Seven out of 9 tumors from this group had invaded at least 2 lymph nodes while only 1 out of 10 tumors in group 2 was lymph node positive. In vitro experiments showed that the interferon-induced increase in Stat1 abundance correlates with increased migration and invasion in cultured cells. When CD74 was overexpressed, it increased cell adhesion on matrigel. This effect was accompanied with a marked increase in the membrane expression of beta-catenin, MUC18, plexins, integrins, and other proteins involved in cell adhesion and cancer metastasis. Taken together, our results show that Stat1/CD74 positive triple-negative tumors are more aggressive and suggest an approach for development of better diagnostics and more targeted therapies for triple negative breast cancer. This article is part of a Special Issue entitled: Proteomics: The clinical link. (C) 2011 Elsevier B.V. All rights reserved.