Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, CINJ 4558, New Brunswick, NJ, 08903, USA.
Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
J Mammary Gland Biol Neoplasia. 2019 Sep;24(3):213-230. doi: 10.1007/s10911-019-09430-6. Epub 2019 May 9.
The SOX genes encode a family of more than 20 transcription factors that are critical regulators of embryogenesis and developmental processes and, when aberrantly expressed, have been shown to contribute to tumor development and progression in both an oncogenic and tumor suppressive role. Increasing evidence demonstrates that the SOX proteins play essential roles in multiple cellular processes that mediate or contribute to oncogenic transformation and tumor progression. In the context of breast cancer, SOX proteins function both as oncogenes and tumor suppressors and have been shown to be associated with tumor stage and grade and poor prognosis. Experimental evidence demonstrates that a subset of SOX proteins regulate critical aspects of breast cancer biology including cancer stemness and multiple signaling pathways leading to altered cell proliferation, survival, and tumor development; EMT, cell migration and metastasis; as well as other tumor associated characteristics. This review will summarize the role of SOX family members as important mediators of tumorigenesis in breast cancer, with an emphasis on the triple negative or basal-like subtype of breast cancer, as well as examine the therapeutic potential of these genes and their downstream targets.
SOX 基因编码一个拥有超过 20 个转录因子的家族,这些转录因子是胚胎发生和发育过程的关键调节因子,并且在异常表达时,已经被证明有助于肿瘤的发生和进展,具有致癌和肿瘤抑制作用。越来越多的证据表明,SOX 蛋白在介导或有助于致癌转化和肿瘤进展的多种细胞过程中发挥重要作用。在乳腺癌中,SOX 蛋白既是癌基因又是肿瘤抑制因子,并且与肿瘤分期和分级以及预后不良有关。实验证据表明,一部分 SOX 蛋白调节乳腺癌生物学的关键方面,包括癌症干细胞特性和多个信号通路,导致细胞增殖、存活和肿瘤发展的改变;EMT、细胞迁移和转移;以及其他与肿瘤相关的特征。这篇综述将总结 SOX 家族成员作为乳腺癌发生的重要介质的作用,重点是三阴性或基底样乳腺癌亚型,并研究这些基因及其下游靶标的治疗潜力。