Aithal Madhuri G S, Rajeswari Narayanappa
Department of Biotechnology, Dayananda Sagar College of Engineering, Bangalore 560 078, India.
J Genet. 2013 Dec;92(3):667-75. doi: 10.1007/s12041-013-0284-5.
The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organisms as diverse as humans and fruit flies. It plays a pivotal role in cell fate determination. Dysregulated Notch signalling is oncogenic, inhibits apoptosis and promotes cell survival. Abnormal Notch signalling is seen in many cancers like T-cell acute lymphoblastic leukaemia, acute myeloid leukaemia and cancers of the breast, cervix, colon, pancreas, skin and brain. Inhibition of Notch signalling leads to growth arrest and differentiation in those cells in which Notch pathway is activated and this represents a new target for cancer therapy. Cancer develops from genome defects, including both genetic and epigenetic alterations. Epigenetics deals with heritable changes in gene function that occur without a change in the DNA sequence. Among various epigenetic alterations such as acetylation, phosphorylation, ubiquitylation and sumoylation, promoter region methylation is considered as an important component in cancer development. Epigenetic alterations can be used as biomarkers in screening, detection, diagnosis, staging and risk stratification of various cancers. DNA methylation can be therapeutically reversed and demethylating drugs have proven to be promising in cancer treatment. This review focusses on the methylation status of genes in Notch signalling pathway from various cancers and how this epigenetic alteration can be used as a biomarker for cancer diagnosis and subsequent treatment.
Notch信号通路是一条在进化上保守的细胞信号通路，参与了从人类到果蝇等多种生物的发育过程。它在细胞命运决定中起着关键作用。Notch信号失调具有致癌性，可抑制细胞凋亡并促进细胞存活。在许多癌症中都可见到异常的Notch信号，如T细胞急性淋巴细胞白血病、急性髓系白血病以及乳腺癌、宫颈癌、结肠癌、胰腺癌、皮肤癌和脑癌等。抑制Notch信号会导致Notch通路被激活的细胞生长停滞并分化，这代表了癌症治疗的一个新靶点。癌症由基因组缺陷引发，包括遗传和表观遗传改变。表观遗传学研究的是在DNA序列不变的情况下基因功能发生的可遗传变化。在诸如乙酰化、磷酸化、泛素化和类泛素化等各种表观遗传改变中，启动子区域甲基化被认为是癌症发展的一个重要组成部分。表观遗传改变可作为生物标志物用于各种癌症的筛查、检测、诊断、分期和风险分层。DNA甲基化可以通过治疗逆转，去甲基化药物已被证明在癌症治疗中具有前景。本综述聚焦于各种癌症中Notch信号通路相关基因的甲基化状态，以及这种表观遗传改变如何作为癌症诊断及后续治疗的生物标志物。
