Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; University of California, San Francisco, Dept. of Pathology, 513 Parnassus Ave., San Francisco, CA 94118, USA.
Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Radiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Biochim Biophys Acta Rev Cancer. 2017 Aug;1868(1):315-332. doi: 10.1016/j.bbcan.2017.06.003. Epub 2017 Jun 15.
The Hedgehog signaling network regulates organogenesis, cell fate, proliferation, survival, and stem cell self-renewal in many mammalian tissues. Aberrant activation of the Hedgehog signaling network is present in ~25% of all cancers, including breast. Altered expression of Hedgehog network genes in the mammary gland can elicit phenotypes at many stages of development. However, synthesizing a cohesive mechanistic model of signaling at different stages of development has been difficult. Emerging data suggest that this difficulty is due, in part, to non-canonical and tissue compartment-specific (i.e., epithelial, versus stromal, versus systemic) functions of Hedgehog network components. With respect to systemic functions, Hedgehog network genes regulate development of endocrine organs that impinge on mammary gland development extrinsically. These new observations offer insight into previously conflicting data, and have bearing on the potential for anti-Hedgehog therapeutics in the treatment of breast cancer.
刺猬信号网络调节许多哺乳动物组织的器官发生、细胞命运、增殖、存活和干细胞自我更新。刺猬信号网络的异常激活存在于所有癌症的~25%中,包括乳腺癌。乳腺中刺猬信号网络基因的表达改变可以在发育的许多阶段引发表型。然而,综合不同发育阶段信号的一致的机制模型一直很困难。新出现的数据表明,这种困难部分归因于刺猬信号网络成分的非经典和组织隔室特异性(即上皮、基质、全身性)功能。就系统性功能而言,刺猬信号网络基因调节内分泌器官的发育,这些器官从外部影响乳腺的发育。这些新的观察结果为以前相互矛盾的数据提供了深入了解,并对使用抗刺猬治疗方法治疗乳腺癌的潜力产生了影响。