Potential role of Notch1 signaling pathway in laryngeal squamous cell carcinoma cell line Hep-2 involving proliferation inhibition, cell cycle arrest, cell apoptosis, and cell migration.
Head and neck cancer is the sixth most common cancer worldwide and laryngeal cancer represents the largest subgroup. However, the molecular mechanism underlying its malignant behavior and progression is not clarified. Accumulating evidence has shown that Notch1 signaling pathway plays a central role in carcinogenesis, but its potential role in regulating the development of laryngeal carcinoma, has not been characterized. Here, we identified that Notch1 signaling pathway was activated in laryngeal carcinoma accompanied with up-regulation of Notch1 and Hes1 expression. Overexpression of Notch1 in laryngeal carcinoma cell line Hep-2 led to suppression of tumor cellular proliferation and arrested cell cycle in the G0/G1 phase and induced cell apoptosis, which were coupled with the down-regulation of cyclin D1, cyclin E, cdk2 and bcl-2 and up-regulation of caspase-3, caspase-9 and p53. Most importantly, up-regulation of Notch1 expression also reduced the migration of Hep-2 cells, which was closely associated with down-regulation of MMP-2 and MMP-9. The finding may lay a foundation for further investigations into the Notch1 signaling pathway as a potential target for laryngeal carcinoma.
Jiao
Jing
J
Department of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Qin
Zhaobing
Z
Li
Sha
S
Liu
Hongtao
H
Lu
Zhaoming
Z
D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D053453:Caspase 9 / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D019927:Cyclin E / Q000096:biosynthesis / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051881:Receptor, Notch1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D000072056:Transcription Factor HES-1; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D053453:Caspase 9; D019938:Cyclin D1; D019927:Cyclin E; D051357:Cyclin-Dependent Kinase 2; D018398:Homeodomain Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; D016159:Tumor Suppressor Protein p53; C497761:NOTCH1 protein, human; C078493:HES1 protein, human; C495894:CDK2 protein, human