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首页> 外文期刊>Molecular and Cellular Biology >p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial-to-Mesenchymal Transition
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p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial-to-Mesenchymal Transition

机译：p66ShcA通过诱导上皮向间质转化促进乳腺癌的可塑性

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Breast cancers are stratified into distinct subtypes, which influence therapeutic responsiveness and patient outcome. Patients with luminal breast cancers are often associated with a better prognosis relative to that with other subtypes. However, subsets of patients with luminal disease remain at increased risk of cancer-related death. A critical process that increases the malignant potential of breast cancers is the epithelial-to-mesenchymal transition (EMT). The p66ShcA adaptor protein stimulates the formation of reactive oxygen species in response to stress stimuli. In this paper, we report a novel role for p66ShcA in inducing an EMT in HER2+ luminal breast cancers. p66ShcA increases the migratory properties of breast cancer cells and enhances signaling downstream of the Met receptor tyrosine kinase in these tumors. Moreover, Met activation is required for a p66ShcA-induced EMT in luminal breast cancer cells. Finally, elevated p66ShcA levels are associated with the acquisition of an EMT in primary breast cancers spanning all molecular subtypes, including luminal tumors. This is of high clinical relevance, as the luminal and HER2 subtypes together comprise 80% of all newly diagnosed breast cancers. This study identifies p66ShcA as one of the first prognostic biomarkers for the identification of more aggressive tumors with mesenchymal properties, regardless of molecular subtype.
机译：乳腺癌被分为不同的亚型，这会影响治疗反应性和患者预后。与其他亚型相比，管腔型乳腺癌患者通常具有更好的预后。但是，腔内疾病患者的子集仍然处于与癌症相关的死亡风险增加的状态。增加乳腺癌恶性潜能的关键过程是上皮-间质转化（EMT）。 p66ShcA衔接蛋白响应压力刺激而刺激活性氧的形成。在本文中，我们报道了p66ShcA在HER2 + 腔内乳腺癌中诱导EMT的新作用。 p66ShcA增加了乳腺癌细胞的迁移特性，并增强了这些肿瘤中Met受体酪氨酸激酶下游的信号传导。而且，p66ShcA诱导的管腔乳腺癌细胞中的EMT需要Met激活。最后，升高的p66ShcA水平与跨越所有分子亚型（包括腔肿瘤）的原发性乳腺癌的EMT获得有关。这具有高度的临床意义，因为管腔和HER2亚型占所有新诊断乳腺癌的80％。这项研究将p66ShcA作为鉴定具有间质特性的更具侵袭性的肿瘤（无论分子亚型如何）的首批预后生物标志物之一。

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