title: Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?
abstract: 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. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs 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 SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.|Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California.
authors.forename: Sangita
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qin
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Biology, Brookhaven National Lab, NewYork.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051880:Receptors, Notch / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051880:Receptors, Notch; D025521:Tumor Suppressor Proteins
keywords: Notch pathway; Notch structure; mutation pattern; squamous cell carcinoma; tumor suppressor