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SHR Neuro Krebs Kardio Lipid

Ress, AL; Stiegelbauer, V; Schwarzenbacher, D; Deutsch, A; Perakis, S; Ling, H; Ivan, C; Calin, GA; Rinner, B; Gerger, A; Pichler, M.
Spinophilin expression determines cellular growth, cancer stemness and 5-flourouracil resistance in colorectal cancer.
Oncotarget. 2014; 5(18):8492-8502 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Deutsch Alexander
Gerger Armin
Lembeck Anna Lena
Perakis Samantha
Pichler Martin
Rinner Beate
Schwarzenbacher Daniela
Stiegelbauer Verena
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Number of Figures: 6
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Abstract:
The putative tumor suppressor gene spinophilin has been involved in cancer progression in several types of cancer. In this study, we explored the prognostic value of spinophilin expression in 162 colon adenocarcinoma patients. In addition, we generated stably expressing spinophilin-directed shRNA CRC cell lines and studied the influence of spinophilin expression on cellular phenotypes and molecular interactions. We independently confirmed that low spinophilin expression levels are associated with poor prognosis in CRC patients (p = 0.038). A reduction of spinophilin levels in p53 wild-type HCT116 and p53-mutated Caco-2 cells led to increased cellular growth rates and anchorage-independent growth (p<0.05). At molecular level, reduced spinophilin levels increased the expression of the transcription factor E2F-1. In addition, we observed an increased formation of tumor spheres, increased number of CD133 positive cells and an increased resistance to 5-flourouracil (p<0.05). Finally, treatment with the de-methylating agent 5-aza-dC increased spinophilin expression in CRC cells (p<0.05), corroborated by a correlation of spinophilin expression and extent of methylated CpG sites in the gene promoter region (p<0.001). In conclusion, gain of aggressive biological properties of CRC cells including cellular growth, cancer stem cell features and 5-flourouracil resistance partly explains the role of spinophilin in CRC.
Find related publications in this database (using NLM MeSH Indexing)
AC133 Antigen -
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - mortality
Adenocarcinoma - pathology
Antigens, CD - metabolism
Antimetabolites, Antineoplastic - therapeutic use
Caco-2 Cells -
Cell Proliferation - drug effects
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
CpG Islands - drug effects
DNA Methylation - drug effects
Dose-Response Relationship, Drug -
Drug Resistance, Neoplasm -
E2F1 Transcription Factor - metabolism
Epigenesis, Genetic - drug effects
Fluorouracil - therapeutic use
Gene Expression Regulation, Neoplastic - drug effects
Glycoproteins - metabolism
HCT116 Cells -
HT29 Cells -
Humans -
Microfilament Proteins - genetics
Microfilament Proteins - metabolism
Mutation -
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Peptides - metabolism
Prognosis -
Promoter Regions, Genetic - drug effects
Proportional Hazards Models -
RNA Interference -
Signal Transduction - drug effects
Spheroids, Cellular -
Time Factors -
Transfection -
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism

Find related publications in this database (Keywords)
colorectal cancer
prognosis
cellular growth
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