ErbB/EGF signaling and EMT in mammary development and breast cancer.
ErbB/EGF signaling and EMT in mammary development and breast cancer.
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DOI：
10.1007/s10911-010-9172-2
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发表时间：
2010-06
影响因子：
2.5
通讯作者：
Strizzi, Luigi
中科院分区：
文献类型：
--
作者：
Hardy, Katharine M.;Booth, Brian W.;Hendrix, Mary J. C.;Salomon, David S.;Strizzi, Luigi
通过同源表皮生长因子（EGF）样肽配体激活受体酪氨酸激酶的ErbB家族构成了控制乳腺癌增殖、存活、血管生成和转移的一组主要的相关信号传导途径。在这方面，各种ErbB受体阻断抗体和特异性酪氨酸激酶抑制剂的临床试验已被证明在治疗这种异质性疾病中部分有效。乳腺癌中上皮向间充质转化（EMT）的胚胎程序的诱导，由此上皮肿瘤细胞转化为更像间充质的表型，促进肿瘤细胞在转移期间的迁移、内渗和外渗。表现出EMT特性的乳腺癌具有高度侵袭性并且对治疗具有抗性。ErbB信号的激活可以调节正常和恶性乳腺上皮细胞中EMT相关的侵袭和迁移，以及调节乳腺发育的离散阶段。这篇综述的目的是总结目前的信息ErbB信号在EMT方面的作用，影响乳腺发育和肿瘤发生过程中上皮细胞的可塑性。这些信息如何有助于改善乳腺癌的治疗方法也将得到解决。
Activation of the ErbB family of receptor tyrosine kinases via cognate Epidermal Growth Factor (EGF)-like peptide ligands constitutes a major group of related signaling pathways that control proliferation, survival, angiogenesis and metastasis of breast cancer. In this respect, clinical trials with various ErbB receptor blocking antibodies and specific tyrosine kinase inhibitors have proven to be partially efficacious in the treatment of this heterogeneous disease. Induction of an embryonic program of epithelial-to-mesenchymal transition (EMT) in breast cancer, whereupon epithelial tumor cells convert to a more mesenchymal-like phenotype, facilitates the migration, intravasation, and extravasation of tumor cells during metastasis. Breast cancers which exhibit properties of EMT are highly aggressive and resistant to therapy. Activation of ErbB signaling can regulate EMT-associated invasion and migration in normal and malignant mammary epithelial cells, as well as modulating discrete stages of mammary gland development. The purpose of this review is to summarize current information regarding the role of ErbB signaling in aspects of EMT that influence epithelial cell plasticity during mammary gland development and tumorigenesis. How this information may contribute to the improvement of therapeutic approaches in breast cancer will also be addressed.
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