Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity. Mol Cancer Res 2016 Sep;14(9):883-91
Date
06/30/2016Pubmed ID
27353029DOI
10.1158/1541-7786.MCR-16-0114Scopus ID
2-s2.0-84987904917 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
UNLABELLED: 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.
IMPLICATIONS: 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.
Author List
Weaver AN, Burch MB, Cooper TS, Della Manna DL, Wei S, Ojesina AI, Rosenthal EL, Yang ESAuthor
Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Carcinoma, Squamous CellFemale
Fibroblast Growth Factor 1
Head and Neck Neoplasms
Humans
Male
Middle Aged
Mouth Neoplasms
Neoplasm Invasiveness
Prognosis
Receptor, Notch1
Signal Transduction
Survival Analysis
