HOX 基因的下游：解释癌症中相互矛盾的肿瘤抑制和致癌功能,International Journal of Cancer

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HOX 基因的下游：解释癌症中相互矛盾的肿瘤抑制和致癌功能
International Journal of Cancer ( IF 5.7 ) Pub Date : 2022-01-26 , DOI: 10.1002/ijc.33949
Richard Morgan ₁ , Keith Hunter ₂ , Hardev S Pandha ₃

Affiliation

HOX 基因是一组高度保守的转录因子，在早期发育中起着关键作用，但在大多数癌症中也高度表达。许多研究发现肿瘤中单个 HOX 基因的表达与包括生存在内的临床参数之间存在很强的关联关系。对于大多数 HOX 基因，高肿瘤表达水平似乎与患者的较差结果相关，并且在某些情况下，这已被证明是由促癌基因和通路的激活引起的。然而，也有许多研究表明某些 HOX 基因具有肿瘤抑制作用，有时得出的结论与早期工作相矛盾。在这篇评论中，我们试图通过关注下游目标来阐明 HOX 基因在癌症中的作用，这些目标在为它们的激活或抑制提供实验证据的研究中确定。在此基础上，大多数 HOX 基因似乎具有促癌功能，但 HOXD10 除外，它专门充当肿瘤抑制因子。HOX 蛋白调节广泛的靶基因，这些靶基因涉及转移、细胞死亡、增殖和血管生成，并激活关键细胞信号通路。此外，对于一些功能相关的目标，这种调节是通过相对较小的 HOX 基因亚组实现的。它专门用作肿瘤抑制因子。HOX 蛋白调节广泛的靶基因，这些靶基因涉及转移、细胞死亡、增殖和血管生成，并激活关键细胞信号通路。此外，对于一些功能相关的目标，这种调节是通过相对较小的 HOX 基因亚组实现的。它专门用作肿瘤抑制因子。HOX 蛋白调节广泛的靶基因，这些靶基因涉及转移、细胞死亡、增殖和血管生成，并激活关键细胞信号通路。此外，对于一些功能相关的目标，这种调节是通过相对较小的 HOX 基因亚组实现的。

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Downstream of the HOX genes: Explaining conflicting tumour suppressor and oncogenic functions in cancer

The HOX genes are a highly conserved group of transcription factors that have key roles in early development, but which are also highly expressed in most cancers. Many studies have found strong associative relationships between the expression of individual HOX genes in tumours and clinical parameters including survival. For the majority of HOX genes, high tumour expression levels seem to be associated with a worse outcome for patients, and in some cases, this has been shown to result from the activation of pro-oncogenic genes and pathways. However, there are also many studies that indicate a tumour suppressor role for some HOX genes, sometimes with conclusions that contradict earlier work. In this review, we have attempted to clarify the role of HOX genes in cancer by focusing on their downstream targets as identified in studies that provide experimental evidence for their activation or repression. On this basis, the majority of HOX genes would appear to have a pro-oncogenic function, with the notable exception of HOXD10, which acts exclusively as a tumour suppressor. HOX proteins regulate a wide range of target genes involved in metastasis, cell death, proliferation and angiogenesis, and activate key cell signalling pathways. Furthermore, for some functionally related targets, this regulation is achieved by a relatively small subgroup of HOX genes.

更新日期：2022-01-26

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