Breast cancer initiation and progression are often observed as the result of dysregulation of normal developmental processes and pathways. Studies focused on normal mammary stem/progenitor cell activity have led to an understanding of how breast cancer cells acquire stemness-associated properties including tumor initiation, survival and multi-lineage differentiation into heterogeneous tumors that become difficult to target therapeutically. Importantly, more recent investigations have provided valuable insight into how key developmental regulators can impact multiple phases of metastasis, where they are repurposed to not only promote metastatic phenotypes such as migration, invasion and EMT at the primary site, but also to regulate the survival, initiation and maintenance of metastatic lesions at secondary organs. Herein, we discuss findings that have led to a better understanding of how embryonic and pluripotency factors contribute not only to normal mammary development, but also to metastatic progression. We further examine the therapeutic potential of targeting these developmental pathways, and discuss how a better understanding of compensatory mechanisms, crosstalk between pathways, and novel experimental models could provide critical insight into how we might exploit embryonic and pluripotency regulators to inhibit tumor progression and metastasis.

中文翻译：

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同一枚硬币的两面：发育途径和多能因子在正常乳腺干细胞和乳腺癌转移中的作用。


乳腺癌的发生和进展通常是正常发育过程和途径失调的结果。关注正常乳腺干/祖细胞活性的研究使人们了解乳腺癌细胞如何获得干性相关特性，包括肿瘤发生、存活和多谱系分化为难以靶向治疗的异质性肿瘤。重要的是，最近的研究为关键的发育调节因子如何影响转移的多个阶段提供了有价值的见解，它们被重新调整用途，不仅可以促进原发部位的转移表型，如迁移、侵袭和 EMT，而且还可以调节生存，次要器官转移病灶的发生和维持。在此，我们讨论的发现使人们更好地了解胚胎和多能因子不仅有助于正常乳腺发育，而且有助于转移进展。我们进一步研究了针对这些发育途径的治疗潜力，并讨论了如何更好地理解补偿机制、途径之间的串扰和新颖的实验模型，可以为我们如何利用胚胎和多能性调节因子抑制肿瘤进展和转移提供重要的见解。