Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro‐oncogenic, typically depending on the cellular context. Squamous cell carcinoma ( SCC ) is a cancer of the squamous cell, which can occur in diverse human tissues. SCC s are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCC s identified marked levels of mutations in NOTCH 1 , implicating Notch signaling pathways in the pathogenesis of SCC s. In this review, evidences highlighting NOTCH 's role in different types of SCC s are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH 1 gene mutations identified from diverse SCC s are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCC s across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCC s and development of therapeutic strategies for these cancers.