Zohourian Nazanin, Coll Erin, Dever Muiread, Sheahan Anna, Burns-Lane Petra, Brown James A L
Department of Biological Science, University of Limerick, V94 T9PX Limerick, Ireland.
Limerick Digital Cancer Research Centre (LDCRC), Health Research Institute (HRI), University of Limerick, V94 T9PX Limerick, Ireland.
Cancers (Basel). 2024 Jul 27;16(15):2677. doi: 10.3390/cancers16152677.
Precision (individualized) medicine relies on the molecular profiling of tumors' dysregulated characteristics (genomic, epigenetic, transcriptomic) to identify the reliance on key pathways (including genome stability and epigenetic gene regulation) for viability or growth, and then utilises targeted therapeutics to disrupt these survival-dependent pathways. Non-mutational epigenetic changes alter cells' transcriptional profile and are a key feature found in many tumors. In contrast to genetic mutations, epigenetic changes are reversable, and restoring a normal epigenetic profile can inhibit tumor growth and progression. Lysine acetyltransferases (KATs or HATs) protect genome stability and integrity, and Tip60 is an essential acetyltransferase due to its roles as an epigenetic and transcriptional regulator, and as master regulator of the DNA double-strand break response. Tip60 is commonly downregulated and mislocalized in many cancers, and the roles that mislocalized Tip60 plays in cancer are not well understood. Here we categorize and discuss Tip60-regulated genes, evaluate Tip60-interacting proteins based on cellular localization, and explore the therapeutic potential of Tip60-targeting compounds as epigenetic inhibitors. Understanding the multiple roles Tip60 plays in tumorigenesis will improve our understanding of tumor progression and will inform therapeutic options, including informing potential combinatorial regimes with current chemotherapeutics, leading to improvements in patient outcomes.
精准（个体化）医学依赖于对肿瘤失调特征（基因组、表观基因组、转录组）进行分子分析，以确定肿瘤存活或生长对关键信号通路（包括基因组稳定性和表观遗传基因调控）的依赖性，然后利用靶向疗法破坏这些依赖生存的信号通路。非突变表观遗传变化会改变细胞的转录谱，是许多肿瘤的一个关键特征。与基因突变不同，表观遗传变化是可逆的，恢复正常的表观遗传谱可以抑制肿瘤生长和进展。赖氨酸乙酰转移酶（KATs或HATs）保护基因组稳定性和完整性，而Tip60是一种重要的乙酰转移酶，因为它作为表观遗传和转录调节因子，以及DNA双链断裂反应的主要调节因子发挥作用。Tip60在许多癌症中通常下调且定位错误，而定位错误的Tip60在癌症中所起的作用尚未完全了解。在这里，我们对Tip60调控的基因进行分类和讨论，根据细胞定位评估与Tip60相互作用的蛋白质，并探索靶向Tip60的化合物作为表观遗传抑制剂的治疗潜力。了解Tip60在肿瘤发生中的多种作用将增进我们对肿瘤进展的理解，并为治疗选择提供依据，包括为与当前化疗药物的潜在联合治疗方案提供依据，从而改善患者预后。
