Cellular plasticity is a phenomenon where cells adopt different identities during development and tissue homeostasis as a response to physiological and pathological conditions. This review provides a general introduction to processes by which cells change their identity as well as the current definition of cellular plasticity in the field of mammary gland biology. Following a synopsis of the evolving model of the hierarchical development of mammary epithelial cell lineages, we discuss changes in cell identity during normal mammary gland development with particular emphasis on the effect of the gestation cycle on the emergence of new cellular states. Next, we summarize known mechanisms that promote the plasticity of epithelial lineages in the normal mammary gland and highlight the importance of the microenvironment and extracellular matrix. A discourse of cellular reprogramming during the early stages of mammary tumorigenesis that follows focuses on the origin of basal-like breast cancers from luminal progenitors and oncogenic signaling networks that orchestrate diverse developmental trajectories of transforming epithelial cells. In addition to the epithelial-to-mesenchymal transition, we highlight events of cellular reprogramming during breast cancer progression in the context of intrinsic molecular subtype switching and the genesis of the claudin-low breast cancer subtype, which represents the far end of the spectrum of epithelial cell plasticity. In the final section, we will discuss recent advances in the design of genetically engineered models to gain insight into the dynamic processes that promote cellular plasticity during mammary gland development and tumorigenesis in vivo.
细胞可塑性是一种细胞在发育和组织稳态过程中，为响应生理及病理条件而获得不同身份的现象。本综述首先概述了细胞改变身份的过程，以及当前乳腺生物学领域对细胞可塑性的定义。在简述乳腺上皮细胞谱系层级发育模型的演变之后，我们探讨了正常乳腺发育过程中细胞身份的变化，特别关注妊娠周期对新细胞状态出现的影响。接着，我们总结了正常乳腺中促进上皮谱系可塑性的已知机制，并强调了微环境和细胞外基质的重要性。随后，文章重点讨论了乳腺肿瘤发生早期阶段的细胞重编程，涉及基底样乳腺癌起源于管腔祖细胞，以及协调转化上皮细胞多样化发育轨迹的致癌信号网络。除上皮-间质转化外，我们还着重阐述了乳腺癌进展过程中，在内在分子亚型转换背景下发生的细胞重编程事件，以及代表上皮细胞可塑性极端谱系的claudin-low乳腺癌亚型的形成。最后一部分，我们将讨论基因工程模型设计的最新进展，这些模型有助于深入理解乳腺发育和体内肿瘤发生过程中促进细胞可塑性的动态过程。
Cellular Plasticity in Mammary Gland Development and Breast Cancer
肿瘤(癌症)患者之家