title: Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity.
abstract: Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system. Results were confirmed using the oral cavity subdivision of the Head and Neck Squamous Cell Carcinoma Cancer (HNSCC) study generated by The Cancer Genome Atlas (TCGA) Research Network. Further characterization of the in vitro phenotype produced by Notch pathway activation in HNSCC cell lines included gene expression, proliferation, cell cycle, migration, invasion, and radiosensitivity. In both UAB and TCGA samples, Notch pathway upregulation was significantly correlated with patient mortality status and with expression of the proinvasive gene FGF1 In vitro Notch activation in HNSCC cells increased transcription of FGF1 and induced a marked increase in cell migration and invasion, which was fully abrogated by FGF1 knockdown. These results reveal that increased Notch pathway signaling plays a role in cancer progression and patient outcomes in OSCC. Accordingly, the Notch-FGF interaction should be further studied as a prognostic biomarker and potential therapeutic target for OSCC.
  
  
  
  Patients with squamous cell carcinoma of the oral cavity who succumb to their disease are more likely to have upregulated Notch signaling, which may mediate a more invasive phenotype through increased FGF1 transcription. Mol Cancer Res; 14(9); 883-91. ©2016 AACR.
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Alice N
authors.initials: AN
authors.lastname: Weaver
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: M Benjamin
authors.initials: MB
authors.lastname: Burch
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Tiffiny S
authors.initials: TS
authors.lastname: Cooper
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Della Manna
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Shi
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Akinyemi I
authors.initials: AI
authors.lastname: Ojesina
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Palo Alto, California.
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama. eyang@uab.edu.
authors.forename: Eddy S
authors.initials: ES
authors.lastname: Yang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D016220:Fibroblast Growth Factor 1