Yap L F, Lee D, Khairuddin Anm, Pairan M F, Puspita B, Siar C H, Paterson I C
Department of Oral Biology & Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Department of Oro-Maxillofacial Surgical & Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Oral Dis. 2015 Oct;21(7):850-7. doi: 10.1111/odi.12309. Epub 2015 Jan 29.
NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid and haematological malignancies. Similar to T-cell acute lymphoblastic leukaemia (T-ALL), early studies suggested a pro-tumorigenic role of NOTCH in head and neck squamous cell carcinoma (HNSCC), mainly based on the increased expression levels of the genes within the pathway. Recently, data from exome sequencing analyses unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by identifying loss-of-function mutations in the NOTCH1 gene in a significant proportion of patients. These data have questioned the accepted role of NOTCH in HNSCC and the possible rationale of targeting NOTCH in this disease. This review summarises the current information on NOTCH signalling in HNSCC and discusses how this pathway can apparently exert opposing effects within the same disease.
NOTCH信号通路在实体瘤和血液系统恶性肿瘤中均可发挥致癌或肿瘤抑制作用。与T细胞急性淋巴细胞白血病（T-ALL）类似，早期研究表明NOTCH在头颈部鳞状细胞癌（HNSCC）中具有促肿瘤作用，这主要基于该信号通路中基因表达水平的升高。最近，外显子组测序分析数据意外地指出，NOTCH在HNSCC中具有肿瘤抑制作用，因为在相当比例的患者中发现了NOTCH1基因的功能丧失突变。这些数据对NOTCH在HNSCC中已被接受的作用以及针对该疾病靶向NOTCH的可能理论依据提出了质疑。本综述总结了目前关于HNSCC中NOTCH信号通路的信息，并讨论了该信号通路如何在同一种疾病中明显发挥相反的作用。
