Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.
Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.
复制标题
DOI：
10.3390/ijms242216407
复制
发表时间：
2023-11-16
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然在了解癌症生物学方面取得了重大进展，但患者生存率的提高是有限的，这强调了创新策略的紧迫性。表观遗传修饰以基因表达的遗传变化为特征，而不改变DNA序列，在产生替代基因亚型中起关键作用。当这些过程出错时，它们会影响癌症的发生、生长、扩散和癌症的发生。在这篇综述中，我们深入研究了蛋白激酶双皮质素样激酶1 （DCLK1）的表观遗传和异构体的细微差别。DCLK1被认为是肿瘤干性的标志，在肿瘤发生中起着关键作用，DCLK1亚型通过替代启动子的使用和剪接形成，可以揭示潜在的治疗接触点。我们的讨论集中在与DCLK1亚型的特定功能有关的最新发现以及通过其两个不同的启动子对其表观遗传调控的普遍理解。值得注意的是，所有DCLK1亚型都保留了它们的激酶结构域，这表明它们的独特功能来自于非激酶机制。因此，我们的研究转向了特异性影响这些DCLK1亚型表观遗传产生的药物。我们假设联合治疗方法，利用特定DCLK1亚型的表观遗传调节因子和DCLK1靶向药物，可能比单独靶向DCLK1的治疗更有效。
While significant strides have been made in understanding cancer biology, the enhancement in patient survival is limited, underscoring the urgency for innovative strategies. Epigenetic modifications characterized by hereditary shifts in gene expression without changes to the DNA sequence play a critical role in producing alternative gene isoforms. When these processes go awry, they influence cancer onset, growth, spread, and cancer stemness. In this review, we delve into the epigenetic and isoform nuances of the protein kinase, doublecortin-like kinase 1 (DCLK1). Recognized as a hallmark of tumor stemness, DCLK1 plays a pivotal role in tumorigenesis, and DCLK1 isoforms, shaped by alternative promoter usage and splicing, can reveal potential therapeutic touchpoints. Our discussion centers on recent findings pertaining to the specific functions of DCLK1 isoforms and the prevailing understanding of its epigenetic regulation via its two distinct promoters. It is noteworthy that all DCLK1 isoforms retain their kinase domain, suggesting that their unique functionalities arise from non-kinase mechanisms. Consequently, our research has pivoted to drugs that specifically influence the epigenetic generation of these DCLK1 isoforms. We posit that a combined therapeutic approach, harnessing both the epigenetic regulators of specific DCLK1 isoforms and DCLK1-targeted drugs, may prove more effective than therapies that solely target DCLK1.
登录
查看更多内容
影响因子：
5.6
作者：
Ma P;Jia G;Song Z
通讯作者：
Song Z
DOI：
10.1016/s1470-2045(21)00288-6
发表时间：
2021-08
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Early Breast Cancer Trialists’ Collaborative group (EBCTCG)
通讯作者：
Early Breast Cancer Trialists’ Collaborative group (EBCTCG)
人乳腺癌中 Nrf-2 和启动子 CpG 甲基化对 p73 基因的转录调控
影响因子：
--
作者：
Lai J;Nie W;Zhang W;Wang Y;Xie R;Wang Y;Gu J;Xu J;Song W;Yang F;Huang G;Cao P;Guan X
通讯作者：
Guan X
影响因子：
--
作者：
Chandrakesan P;Weygant N;May R;Qu D;Chinthalapally HR;Sureban SM;Ali N;Lightfoot SA;Umar S;Houchen CW
通讯作者：
Houchen CW
影响因子：
29.4
作者：
Dandawate, Prasad;Ghosh, Chandrayee;Dhar, Animesh
通讯作者：
Dhar, Animesh