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Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2021-09-02 , DOI: 10.1007/s12195-021-00694-9
Busra Buyuk 1 , Sha Jin 1 , Kaiming Ye 1
Affiliation  

Breast carcinoma is highly metastatic and invasive. Tumor metastasis is a convoluted and multistep process involving tumor cell disseminating from their primary site and migrating to the secondary organ. Epithelial-mesenchymal transition (EMT) is one of the crucial steps that initiate cell progression, invasion, and metastasis. During EMT, epithelial cells alter their molecular features and acquire a mesenchymal phenotype. The regulation of EMT is centered by several signaling pathways, including primary mediators TGF-β, Notch, Wnt, TNF-α, Hedgehog, and RTKs. It is also affected by hypoxia and microRNAs (miRNAs). All these pathways are the convergence on the transcriptional factors such as Snail, Slug, Twist, and ZEB1/2. In addition, a line of evidence suggested that EMT and cancer stem like cells (CSCs) are associated. EMT associated cancer stem cells display mesenchymal phenotypes and resist to chemotherapy or targeted therapy. In this review, we highlighted recent discoveries in these signaling pathways and their regulation in breast cancer metastasis and invasion. While the clinical relevance of EMT and breast cancers remains controversial, we speculated a convergent signaling network pivotal to elucidating the transition of epithelial to mesenchymal phenotypes and onset of metastasis of breast cancer cells.



中文翻译:

导致乳腺癌转移的上皮间质转化信号通路

乳腺癌具有高度转移性和侵袭性。肿瘤转移是一个复杂的多步骤过程,涉及肿瘤细胞从原发部位播散并迁移到次要器官。上皮间质转化(EMT)是启动细胞进展、侵袭和转移的关键步骤之一。在 EMT 过程中,上皮细胞改变其分子特征并获得间充质表型。EMT 的调节以多种信号通路为中心,包括主要介质 TGF-β、Notch、Wnt、 TNF-α、Hedgehog 和 RTK。它还受到缺氧和 microRNA (miRNA) 的影响。所有这些途径都是 Snail、Slug、Twist 和 ZEB1/2 等转录因子的汇聚。此外,一系列证据表明 EMT 与癌症干细胞样细胞 (CSC) 相关。EMT 相关的癌症干细胞表现出间充质表型并对化疗或靶向治疗产生抵抗。在这篇综述中,我们重点介绍了这些信号通路的最新发现及其对乳腺癌转移和侵袭的调节。虽然 EMT 和乳腺癌的临床相关性仍存在争议,但我们推测汇聚信号网络对于阐明上皮细胞表型向间充质表型的转变以及乳腺癌细胞转移的发生至关重要。

更新日期:2021-09-03
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