Molecular Regulation of Cell Cycle and Cell Cycle-Targeted Therapies in Head and Neck Squamous Cell Carcinoma (HNSCC)

2018 ◽  
pp. 185-227
Author(s):  
Elena V. Demidova ◽  
Waleed Iqbal ◽  
Sanjeevani Arora
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Regulation ◽  
Regulation Of Cell Cycle

scholarly journals Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

2017 ◽  
Vol 392 ◽  
pp. 71-82 ◽  
Author(s):  
Ming Zhang ◽  
Ratnakar Singh ◽  
Shaohua Peng ◽  
Tuhina Mazumdar ◽  
Vaishnavi Sambandam ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Lim Protein ◽  
Cell Cycle Inhibitors

scholarly journals Radiosensitizing effect of galunisertib, a TGF-ß receptor I inhibitor, on head and neck squamous cell carcinoma in vitro

2022 ◽  
Author(s):  
Bernhard J. Jank ◽  
Teresa Lenz ◽  
Markus Haas ◽  
Lorenz Kadletz-Wanke ◽  
Nicholas J. Campion ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Metabolic Activity ◽  
Neck Squamous Cell Carcinoma ◽  
Radiosensitizing Effect

SummaryBackground. Resistance to radiation therapy poses a major clinical problem for patients suffering from head and neck squamous cell carcinoma (HNSCC). Transforming growth factor ß (TGF-ß) has emerged as a potential target. This study aimed to investigate the radiosensitizing effect of galunisertib, a small molecule TGF-ß receptor kinase I inhibitor, on HNSCC cells in vitro. Methods. Three HNSCC cell lines were treated with galunisertib alone, or in combination with radiation. Of those three cell lines, one has a known inactivating mutation of the TGF-ß pathway (Cal27), one has a TGF-ß pathway deficiency (FaDu) and one has no known alteration (SCC-25). The effect on metabolic activity was evaluated by a resazurin-based reduction assay. Cell migration was evaluated by wound-healing assay, clonogenic survival by colony formation assay and cell cycle by FACS analysis. Results. Galunisertib reduced metabolic activity in FaDu, increased in SCC-25 and had no effect on CAL27. Migration was significantly reduced by galunisertib in all three cell lines and showed additive effects in combination with radiation in CAL27 and SCC-25. Colony-forming capabilities were reduced in SCC-25 by galunisertib and also showed an additive effect with adjuvant radiation treatment. Cell cycle analysis showed a reduction of cells in G1 phase in response to galunisertib treatment. Conclusion. Our results indicate a potential antineoplastic effect of galunisertib in HNSCC with intact TGF-ß signaling in combination with radiation.

Identification of novel prognostic biomarkers in head and neck squamous cell carcinoma using bioinformatics analysis

2020 ◽  
Vol 23 ◽  
Author(s):  
Yi Ding ◽  
Min Li ◽  
Tuersong Tayier ◽  
Long Chen ◽  
ShuMei Feng
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Interaction Network ◽  
Tumor Grade ◽  
Neck Squamous Cell Carcinoma ◽  
Hub Genes ◽  
Key Genes

Background: : Head and neck squamous cell carcinoma (HNSCC) is a common cancer that is characterized by a complex pathogenesis. Only limited data are available on the primary pathogenic genes and pathways in HNSCC. Objective: This study aimed to identify potential biomarkers of HNSCC and explore its underlying mechanisms. Methods: We screened differentially expressed genes (DEGs) using the Gene Expression Omnibus(GEO) database. Gene Ontology (GO) and Reactome pathway enrichment were analyzed using the STRING database. The protein-protein interaction network of the DEGs was reconstructed using Cytoscape software in STRING. The ONCOMINE and UNLCAN databases were used to identify the expression of hub genes. In addition, we employed UNLCAN to correlate tumor grade with key genes. Results: Finally, the effect of hub genes on overall survival (OS) was analyzed using the Kaplan-Meier method. In total, 22 DEGs were identified, These were related to the mitotic cell cycle, mitotic G1-G1, and S phases, G2/M transition, NOTCH signaling, and regulation of TP53 activity. Seven hub genes were screened with Cytoscape. Increased expression of five hub genes (AURKA, BIRC5, MKI67, UBE2C, and TOP2A) was related to a higher tumor grade and worse OS. Conclusion: We have identified five key genes that may help us understand the carcinogenic mechanisms related to the cell cycle in HNSCC. These genes may be used as biomarkers for survival and treatment of HNSCC.

scholarly journals Recent Advances in Biomarkers and Potential Targeted Therapies in Head and Neck Squamous Cell Carcinoma

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Eric J. Yavrouian ◽  
Uttam K. Sinha
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Neck Squamous Cell Carcinoma ◽  
Oncogenic Viruses ◽  
Upper Aerodigestive Tract

Head and neck squamous cell carcinoma (HNSCC) is a devastating tumor of the upper aerodigestive tract with no significant change in treatment modality or improvement in survival over the last several decades. Biomarkers are important biological molecules that can be utilized in tumor detection, prognosis, and as targeted therapies. There are several important biomarkers and potential targets in the forefront, including biomarkers of tumorigenesis, signal transduction molecules, proteins involved in angiogenesis, and oncogenic viruses. The clinical applications of these biomarkers are in various states from in vitro and in vivo models, phase II and III clinical trials, to accepted modes of treatment in patients with HNSCC. Given the potential improvement in prognosis that biomarkers and their targeted therapies may have on the treatment of HNSCC, their investigation is both important and essential.

scholarly journals Overexpression of TRIM24 Stimulates Proliferation and Glucose Metabolism of Head and Neck Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hongming Wang ◽  
Weishuang Xue ◽  
Xuejun Jiang
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Glucose Metabolism ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Head And Neck ◽  
Squamous Cell ◽  
Colony Formation ◽  
Glucose Deprivation ◽  
Neck Squamous Cell Carcinoma

TRIM24 (Tripartite Motif Containing 24) is a recently identified oncogene overexpressed in various cancers. However, the molecular mechanism of TRIM24 in the progression of head and neck squamous cell carcinoma (HNSCC) remains ambiguous. In the present study, we analyzed the expression pattern of TRIM24 in 100 HNSCC tissues and found that TRIM24 was overexpressed in 43/100 HNSCC cases. Significant association was found between TRIM24 overexpression and tumor-node-metastasis (TNM) stage (p=0.0034) and T stage (p=0.0048). Furthermore, we overexpressed and knocked down TRIM24 in Detroit 562 and FaDu cell lines, respectively. TRIM24 overexpression promoted proliferation, colony formation, and invasion, while TRIM24 depletion inhibited proliferation, colony formation, and invasion. Further studies showed that TRIM24 facilitated cell cycle transition and upregulated cyclin D1 and p-Rb. In addition, we found that GLUT3, a key protein involved in regulating glucose metabolism, was altered in HNSCC cells overexpressing TRIM24. We demonstrated that TRIM24 overexpression increased glucose uptake ATP production. Overexpression of TRIM24 increases cell sensitivity to glucose deprivation in Detroit cells. Depleting TRIM24 in FaDu cells demonstrated the opposite results. We also showed that TRIM24 could bind to the promoter region of cyclin D1. In conclusion, TRIM24 is upregulated in HNSCC and promotes HNSCC cell growth and invasion through modulation of cell cycle, glucose metabolism, and GLUT3, making TRIM24 a potential oncoprotein in HNSCC.

scholarly journals Selected genetic determinants of head and neck squamous cell carcinoma including of some genes for cell cycle control and DNA repair

2018 ◽  
Vol 72 ◽  
pp. 526-539
Author(s):  
Karolina Gołąbek ◽  
Jadwiga Gaździcka ◽  
Zofia Ostrowska
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Dna Repair ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Genetic Predisposition ◽  
Cell Cycle Control ◽  
Neck Squamous Cell Carcinoma ◽  
Specific Gene

The head and neck squamous cell carcinoma, which are located in different anatomical structures like: oral cavity, throat and larynx, are becoming a major clinical problem due to the ever increasing number of cases and also due to difficulty with treating patients. Among the risks factors associated with that group of cancers the exogenous factors such as: exposure to carcinogens in tobacco smoke, alcohol abuse, impropriety dietary habits, poor oral hygiene as well as infection with the human papillomavirus and infection with Epstein-Barr virus, are well-known and had been described. The second potential group of the risk factors are endogenous factors such as genetic predisposition and disorder immune system. Recently, in view of technical progress of molecular biology, the aim of researches became the polymorphisms the most of genes encoding proteins with a wide variety of functions. In the present study we comprehensively discussed the problems associated with the molecular basis of development the head and neck squamous-cell carcinoma. More specifically, this study investigated the single nucleotide polymorphisms and mutations of genes involved in cell cycle control (TP53, p73, CDKN1A, CDKN2A, MDM2, E2F1, E2F2 and EGFR) and in different pathways of DNA repair (XPA, XPB, XPC, XPD, XPF, XPG, ERCC1, OGG1, XRCC1, NBS1, RAD51, BRCA2, XRCC2, XRCC3, XRCC5 and XRCC6). The results of studies indicate a mixed picture of genetic predisposition of the head and neck cancers. Nevertheless, it can be observed that a single polymorphism of specific gene moderately influence on the pathogenesis of that cancers. Commonly, coexistence of few polymorphism at the same time may increase the cancer risk significantly. It is undeniable that the issues discussed in that article should be the subject of further analysis.

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