Oncogenic role of PDK4 in human colon cancer cells

Background: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared wi...

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Veröffentlicht in:British journal of cancer Jg. 116; H. 7; S. 930 - 936
Hauptverfasser: Leclerc, D, Pham, D N T, Lévesque, N, Truongcao, M, Foulkes, W D, Sapienza, C, Rozen, R
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 28.03.2017
Nature Publishing Group
Schlagworte:
631/67/2327
692/53/2421
Animals
Apoptosis
Biobanks
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinogenesis
Case-Control Studies
Cell Movement
Cell Proliferation
Colonic Neoplasms - genetics
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Colorectal cancer
Dehydrogenases
DNA Methylation
Drug Resistance
Epidemiology
Female
Follow-Up Studies
Gene Expression Regulation, Enzymologic
Glucose
Hospitals
Human subjects
Humans
Immunoenzyme Techniques
Kinases
Male
Medical research
Metabolism
Mice
Middle Aged
Molecular Diagnostics
Molecular Medicine
Neoplasm Staging
Oncology
Phosphorylation
Prognosis
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
RNA, Small Interfering - genetics
Tumor Cells, Cultured
Canada
United States > US
Montreal Quebec Canada
hypoxia
cancer detection
RNAi
cancer target
methylation
glycolysis
pyrosequencing
ISSN:0007-0920, 1532-1827, 1532-1827
Online-Zugang:Volltext
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Zusammenfassung:Background: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied. Methods: PDK4 methylation in blood of CRC patients and controls was evaluated by pyrosequencing. PDK4 expression in human colon carcinoma cells was down-regulated by RNAi. Cellular migration and invasion, apoptosis and qRT-PCR of key genes were assessed. Results: Pyrosequencing revealed decreased methylation of the same four consecutive CpGs in the blood of patients compared with controls. Cellular migration and invasion were reduced and apoptosis was increased following transient or stable inhibition of PDK4 . Expression of vimentin, HIF-1 and VEGFA was reduced. Conclusions: These studies demonstrate the involvement of PDK4 in transformation. Methylation assessment of PDK4 in the blood may be useful for non-invasive CRC detection. PDK4 should be considered as a target for development of anticancer strategies and therapies
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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/bjc.2017.38