Pires Bruno Ricardo Barreto, DE Amorim Ísis Salviano Soares, Souza Layane Duarte E, Rodrigues Juliana Alves, Mencalha Andre Luiz
Stem Cell Laboratory, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil.
Biophysics and Biometry Department, Roberto Alcantara Gomes Biology Institute, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.
Anticancer Res. 2016 Nov;36(11):5681-5691. doi: 10.21873/anticanres.11151.
Breast cancer is a public health problem both in developing and developed countries. The breast cancer stem cell (BCSC) hypothesis has grown in the cancer research community. These BCSCs comprise of a small subpopulation of cells within the tumor mass which exhibit stem cell-like characteristics and have emerged as being responsible for tumor development, recurrence and metastasis in BC. The complexity of control of gene expression in BCSC is commonly driven by a myriad of signaling pathways triggered by extracellular signals, mutations and epigenetic control. Thus, some signaling pathways have been highlighted in BC, especially those linked to stem cell phenotype, such as nuclear factor-kappa B, signal transducer and activator of transcription 3, wingless-type MMTV integration site family (Wnt)/β-catenin, Hedgehog and NOTCH. Moreover, these BCSCs can also be influenced by the tumor microenvironment, for instance, hypoxic areas. Given the importance of signaling pathways and tumor microenvironment for breast cancer, this review focuses on the relationship between cellular signaling and BCSCs and its therapeutic implications.
乳腺癌在发展中国家和发达国家都是一个公共卫生问题。乳腺癌干细胞（BCSC）假说在癌症研究领域日益受到关注。这些BCSC是肿瘤块内一小部分具有干细胞样特征的细胞亚群，已被认为是乳腺癌肿瘤发生、复发和转移的原因。BCSC中基因表达调控的复杂性通常由细胞外信号、突变和表观遗传控制引发的众多信号通路驱动。因此，一些信号通路在乳腺癌中受到关注，特别是那些与干细胞表型相关的通路，如核因子-κB、信号转导和转录激活因子3、无翅型MMTV整合位点家族（Wnt）/β-连环蛋白、Hedgehog和NOTCH。此外，这些BCSC也会受到肿瘤微环境的影响，例如缺氧区域。鉴于信号通路和肿瘤微环境对乳腺癌的重要性，本综述重点关注细胞信号与BCSC之间的关系及其治疗意义。
