Upregulation of cell cycle genes in head and neck cancer patients may be antagonized by erufosine's down regulation of cell cycle processes in OSCC cells

Oncotarget
Shariq S AnsariMartin R Berger

Abstract

The TCGA database was analyzed to identify deregulation of cell cycle genes across 24 cancer types and ensuing effects on patient survival. Pan-cancer analysis showed that head and neck squamous cell carcinoma (HNSCC) ranks amongst the top four cancers showing deregulated cell cycle genes. Also, the median gene expression of all CDKs and cyclins in HNSCC patient samples was higher than that of the global gene expression. This was verified by IHC staining of CCND1 from HNSCC patients. When evaluating the quartiles with highest and lowest expression, increased CCND1/CDK6 levels had negative implication on patient survival. In search for a drug, which may antagonize this tumor profile, the potential of the alkylphosphocholine erufosine was evaluated against cell lines of the HNSCC subtype, oral squamous cell carcinoma (OSCC) usingin-vitroandin-vivoassays. Erufosine inhibited growth of OSCC cell lines concentration dependently. Initial microarray findings revealed that cyclins and CDKs were down-regulated concentration dependently upon exposure to erufosine and participated in negative enrichment of cell cycle processes. These findings, indicating a pan-cdk/cyclin inhibition by erufosine, were verified at both, mRNA and protein lev...Continue Reading

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Citations

Jun 7, 2019·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Omar KujanCamile S Farah
Oct 9, 2019·International Journal of Molecular Sciences·Marineta KovachevaMartin R Berger
May 16, 2020·Frontiers in Pharmacology·Ferda KaleağasıoğluMartin R Berger
Oct 2, 2020·Journal of Molecular Histology·Vanessa Sousa Nazare GuimaraesClarissa Araújo Gurgel Rocha
Oct 16, 2018·Anti-cancer Agents in Medicinal Chemistry·Ferda KaleağasıoğluMartin R Berger

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Datasets Mentioned

BETA
GSE96599

Methods Mentioned

BETA
xenograft
xenografts
Chip
PCR
flow cytometry

Software Mentioned

gplots
Bioconductor
GraphPad Prism
R
GOstats
limma

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