Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.18632/oncotarget.2329
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- Führende Autor*innen der Med Uni Graz
- Lembeck Anna Lena
- Pichler Martin
- Stiegelbauer Verena
- Co-Autor*innen der Med Uni Graz
- Deutsch Alexander
- Gerger Armin
- Hasenleithner Samantha
- Ninaus Daniela
- Rinner Beate
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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