title: PDK1 promotes tumor cell proliferation and migration by enhancing the Warburg effect in non-small cell lung cancer.
abstract: Tumor cells prefer glycolysis (Warburg effect) during the proliferation and metastasis. The precise mechanism remains largely unknown. Here, we demonstrated that pyruvate dehydrogenase kinase 1 (PDK1) was a critical enzyme that functioned as an oncogene to promote non-small cell lung cancer (NSCLC) growth and metastasis. We discovered that PDK1 expression was significantly upregulated in NSCLC tissues and correlated with advanced T stage. Moreover, high expression of PDK1 was an independent prognostic factor of NSCLC. Ectopic overexpression of PDK1 promoted cell proliferation and inhibited apoptosis. Also it was shown that PDK1 increased the cell mobility when Transwell assay was performed. Further experiments indicated that PDK1 had a central role in metabolic reprogramming by phosphorylating pyruvate dehydrogenase, leading to enhanced Warburg effect. Collectively, our data reveal a new function for PDK1, which could be used to indicate the prognosis of NSCLC, and provide targeted therapeutic strategy for clinical treatment.
authors.affiliation: Department of Pneumology, Heilongjiang Province Hospital, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pneumology, Heilongjiang Province Hospital, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Yin
mesh_terms: D000072283:A549 Cells; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases