Project description:We hypothesized that DKK3 may exert oncogenic function supecifically in head and neck squamous cell carcinoma (HNSCC). DKK3 overexpression in HNSCC cell resulted in elevated cellular proliferation, migration, invasion and in vivo tumor growth. This elevated malignant properties was not driven by Wnt/beta-catenin pathway.
Project description:Head and neck squamous cell carcinoma(HNSCC) is a significant cause of mortality, while the underlying mechanism remains unclear. Recent studies indicate that KIF2C could play a vital role in tumor proliferation and metastasis. Our results demonstrate that KIF2C is highly expressed at both the mRNA and protein levels in HNSCC samples compared to normal samples. Gene ontol-ogy and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that differentially expressed genes were enriched in processes or pathways related to cell adhesion and cell mitosis in HNSCC. Additionally, a protein-protein interaction network was established, identifying KIF2C as a potential hub gene in HNSCC. Cell phenotype assays showed that KIF2C knockdown reduces cell migration and invasion ability and exhibited cell cycle arrest, high proportion of abnormal cell apoptosis and cell chromosome division mismatches in HNSCC cell line. RNA-seq and RT-PCR assay results revealed that KIF2C knockdown influenced the expression levels of PDGFA, CCNA1, RRM1, CCND2, CAV1, EGFR, SNAI2, KRT5, KRT14, NID1, TP63. TGFBR2, TGFB2, ICAM1, ITGB2, CDH2, CDH5, FN1. And KIF2C knockdown also decreased the phos-phorylation of mTOR, AKT, and ERK. Furthermore, in vivo studies have demonstrated that KIF2C knockdown significantly inhibits tumor proliferation in nude mice. As such, our study highlights the potential therapeutic role of KIF2C for HNSCC treatment.
Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue comparative analysis of gene expression profiles of head and neck squamous cell carcinoma and Head and Neck normal tissue
Project description:Protein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular, PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKCÂ expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN. Experiment Overall Design: 9 samples composed of treated replicates at three time points
Project description:This SuperSeries is composed of the following subset Series: GSE11929: Identification of a subgroup of head and neck cancers lacking numerical chromosomal aberrations GSE11931: Copy Number Alterations in HNSCC with or without Oncogene Expressing Human Papillomavirus Refer to individual Series
Project description:The differential diagnosis between head & neck squamous cell carcinomas and lung squamous cell carcinomas is often unresolved because the histologic appearance of these two tumor types is similar. In the development of a gene expression profile test (GEP-HN-LS) that distinguishes these 2 cancer types, a collection of poorly differentiated primary and metastatic tumor specimens were used. Here we describe 76 such tumor specimens that were used for validation of GEP-HN-LS. The specimens are either head & neck squamous cell carcinomas or lung squamous cell carcinomas.
Project description:The differential diagnosis between head & neck squamous cell carcinomas and lung squamous cell carcinomas is often unresolved because the histologic appearance of these two tumor types is similar. In the development of a gene expression profile test (GEP-HN-LS) that distinguishes these 2 cancer types, a collection of poorly differentiated primary and metastatic tumor specimens were used. Here we describe 76 such tumor specimens that were used for validation of GEP-HN-LS. The specimens are either head & neck squamous cell carcinomas or lung squamous cell carcinomas. All tissue specimens were formalin fixed paraffin embedded specimens. Gene expression was profiled using Affymetrix GeneChip platform.
Project description:We hypothesized that DKK3 may exert oncogenic function supecifically in head and neck squamous cell carcinoma (HNSCC). DKK3 knockdown in HNSCC cell resulted in decreased cellular proliferation, migration, invasion and in vivo tumor growth.