Animal Molecular and Cellular Biology Group (AMCB), Louvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, Louvain-la-Neuve, Belgium.
Heart Failure Research Center, Amsterdam University Medical Center (AMC), Universiteit van Amsterdam, Amsterdam, the Netherlands.
Biochim Biophys Acta Rev Cancer. 2022 Jul;1877(4):188747. doi: 10.1016/j.bbcan.2022.188747. Epub 2022 Jun 5.
More than 25 years ago, the first literature records mentioned HOXA1 expression in human breast cancer. A few years later, HOXA1 was confirmed as a proper oncogene in mammary tissue. In the following two decades, molecular data about the mode of action of the HOXA1 protein, the factors contributing to activate and maintain HOXA1 gene expression and the identity of its target genes have accumulated and provide a wider view on the association of this transcription factor to breast oncogenesis. Large-scale transcriptomic data gathered from wide cohorts of patients further allowed refining the relationship between breast cancer type and HOXA1 expression. Several recent reports have reviewed the connection between cancer hallmarks and the biology of HOX genes in general. Here we take HOXA1 as a paradigm and propose an extensive overview of the molecular data centered on this oncoprotein, from what its expression modulators, to the interactors contributing to its oncogenic activities, and to the pathways and genes it controls. The data converge to an intricate picture that answers questions on the multi-modality of its oncogene activities, point towards better understanding of breast cancer aetiology and thereby provides an appraisal for treatment opportunities.
25 多年前，第一篇文献记录了 HOXA1 在人类乳腺癌中的表达。几年后，HOXA1 被确认为乳腺组织中的合适癌基因。在接下来的二十年里，关于 HOXA1 蛋白作用模式的分子数据、促进和维持 HOXA1 基因表达的因素及其靶基因的特性不断积累，为该转录因子与乳腺癌发生的关联提供了更广泛的视角。从大量患者群体中收集的大规模转录组数据进一步完善了乳腺癌类型与 HOXA1 表达之间的关系。最近有几项研究综述了癌症特征与 HOX 基因生物学之间的一般联系。在这里，我们以 HOXA1 为例，提出了一个关于该癌蛋白的分子数据的广泛概述，从其表达调节剂到促进其致癌活性的相互作用因子，以及它所控制的途径和基因。这些数据汇聚成一幅复杂的图景，回答了关于其致癌基因活性的多模态性的问题，为更好地理解乳腺癌的病因学提供了依据，并为治疗机会提供了评估。
