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ShcA衔接蛋白是乳腺癌进展的关键调节因子。

The ShcA adaptor protein is a critical regulator of breast cancer progression.

作者信息

Ursini-Siegel Josie, Muller William J

机构信息

Department of Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

Cell Cycle. 2008 Jul 1;7(13):1936-43. doi: 10.4161/cc.7.13.6205. Epub 2008 Apr 24.

Abstract

Breast cancer affects 1 in 8 North American women throughout their lifetime and is the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease whose progression from hyperplasia to ductal carcinoma in situ and invasive carcinoma is regulated by the aberrant expression of multiple mediators; including growth factors, cytokines, chemokines and proteases that are produced both by the mammary tumor itself and the adjacent reactive stroma. These signals promote tumor cell proliferation, survival, establishment of a tumor vasculature, invasion and ultimately metastasis to secondary organs. Moreover, the ability of the tumor to create a state of local immune suppression allows tumor cells to evade clearance by the immune system. ShcA is an adaptor protein that relays extracellular signals downstream of receptor tyrosine kinases. Clinical studies suggest that activation of the ShcA signaling pathway is associated with poor patient prognosis. Moreover, recent studies with transgenic mouse models have clearly demonstrated the importance of tumor autonomous ShcA signaling, as well as signaling in cells comprising the tumor microenvironment, for the regulation of these biological processes, which contribute to breast cancer development and metastasis.

摘要

北美每8名女性中就有1人在其一生中会患乳腺癌,乳腺癌是癌症相关死亡的第二大主要原因。乳腺癌是一种异质性疾病,其从增生发展到原位导管癌和浸润性癌的过程受多种介质异常表达的调控;这些介质包括生长因子、细胞因子、趋化因子和蛋白酶,它们由乳腺肿瘤本身和相邻的反应性基质产生。这些信号促进肿瘤细胞增殖、存活、肿瘤血管生成、侵袭并最终转移至继发器官。此外,肿瘤产生局部免疫抑制状态的能力使肿瘤细胞能够逃避免疫系统的清除。ShcA是一种衔接蛋白,可在受体酪氨酸激酶下游传递细胞外信号。临床研究表明,ShcA信号通路的激活与患者预后不良相关。此外,最近对转基因小鼠模型的研究清楚地证明了肿瘤自主性ShcA信号以及肿瘤微环境中细胞的信号对于调节这些促成乳腺癌发生和转移的生物学过程的重要性。

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