The human family of Potassium (K+) Channel Tetramerization Domain (KCTD) proteins counts 25 members, and a significant number of them are still only partially characterized. While some of the KCTDs have been linked to neurological disorders or obesity, a growing tally of KCTDs are being associated with cancer hallmarks or involved in the modulation of specific oncogenic pathways. Indeed, the potential relevance of the variegate KCTD family in cancer warrants an updated picture of the current knowledge and highlights the need for further research on KCTD members as either putative therapeutic targets, or diagnostic/prognostic markers. Homology between family members, capability to participate in ubiquitination and degradation of different protein targets, ability to heterodimerize between members, role played in the main signalling pathways involved in development and cancer, are all factors that need to be considered in the search for new key players in tumorigenesis. In this review we summarize the recent published evidence on KCTD members’ involvement in cancer. Furthermore, by integrating this information with data extrapolated from public databases that suggest new potential associations with cancers, we hypothesize that the number of KCTD family members involved in tumorigenesis (either as positive or negative modulator) may be bigger than so far demonstrated.

中文翻译：

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KCTD蛋白在癌症中的新兴作用

钾 (K+) 通道四聚结构域 (KCTD) 蛋白的人类家族共有 25 个成员，其中很大一部分仍只是部分表征。虽然一些 KCTD 与神经系统疾病或肥胖有关，但越来越多的 KCTD 与癌症标志相关或参与特定致癌途径的调节。事实上，多样化的 KCTD 家族在癌症中的潜在相关性需要对当前知识进行更新，并强调需要进一步研究 KCTD 成员作为推定的治疗靶点或诊断/预后标志物。家族成员之间的同源性，参与泛素化和降解不同蛋白质靶标的能力，成员之间异二聚化的能力，在涉及发育和癌症的主要信号通路中发挥的作用，都是在寻找肿瘤发生的新关键参与者时需要考虑的因素。在这篇综述中，我们总结了最近发表的关于 KCTD 成员参与癌症的证据。此外，通过将这些信息与从公共数据库推断的数据相结合，这些数据表明与癌症有新的潜在关联，我们假设参与肿瘤发生的 KCTD 家族成员的数量（作为正调节剂或负调节剂）可能比目前所证明的要多。