title: Phosphorylation of pyruvate kinase M2 and lactate dehydrogenase A by fibroblast growth factor receptor 1 in benign and malignant thyroid tissue.
abstract: BACKGROUND
  Lactate dehydrogenase A (LDHA) and Pyruvate Kinase M2 (PKM2) are important enzymes of glycolysis. Both of them can be phosphorylated and therefore regulated by Fibroblast growth factor receptor 1 (FGFR1). While phosphorylation of LDHA at tyrosine10 leads to tetramerization and activation, phosphorylation of PKM2 at tyrosine105 promotes dimerization and inactivation. Dimeric PKM2 is found in the nucleus and regulates gene transcription. Up-regulation and phosphorylation of LDHA and PKM2 contribute to faster proliferation under hypoxic conditions and promote the Warburg effect.
  
  
  METHODS
  Using western blot and SYBR Green Real time PCR we investigated 77 thyroid tissues including 19 goiter tissues, 11 follicular adenomas, 16 follicular carcinomas, 15 papillary thyroid carcinomas, and 16 undifferentiated thyroid carcinomas for total expression of PKM2, LDHA and FGFR1. Additionally, phosphorylation status of PKM2 and LDHA was analysed. Inhibition of FGFR was performed on FTC133 cells with SU-5402 and Dovitinib.
  
  
  RESULTS
  All examined thyroid cancer subtypes overexpressed PKM2 as compared to goiter. LDHA was overexpressed in follicular and papillary thyroid cancer as compared to goiter. Elevated phosphorylation of LDHA and PKM2 was detectable in all analysed cancer subtypes. The highest relative phosphorylation levels of PKM2 and LDHA compared to overall expression were found in undifferentiated thyroid cancer. Inhibition of FGFR led to significantly decreased phosphorylation levels of PKM2 and LDHA.
  
  
  CONCLUSIONS
  Our data shows that overexpression and increased phosphorylation of PKM2 and LHDA is a common finding in thyroid malignancies. Phospho-PKM2 and Phospho-LDHA could be valuable tumour markers for thyroglobulin negative thyroid cancer.
authors.affiliation: Department of General, Visceral and Vascular Surgery, Faculty of Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany. pkachel@ukaachen.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Kachel
authors.affiliation: Department of Internal Medicine II, Faculty of Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany. bogusz.trojanowicz@uk-halle.de.
authors.forename: Bogusz
authors.initials: B
authors.lastname: Trojanowicz
authors.affiliation: Department of General, Visceral and Vascular Surgery, Faculty of Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany. carsten.sekulla@uk-halle.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Sekulla
authors.affiliation: Department of General, Visceral and Vascular Surgery, Faculty of Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany. hanna.prenzel@uk-halle.de.
authors.forename: Hanna
authors.initials: H
authors.lastname: Prenzel
authors.affiliation: Department of General, Visceral and Vascular Surgery, Faculty of Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany. henning.dralle@uk-halle.de.
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.affiliation: Department of General, Visceral and Vascular Surgery, Faculty of Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany. hoang-vu@uk-halle.de.
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
mesh_terms: D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology*; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D008565:Membrane Proteins; D012333:RNA, Messenger; D051496:Receptor, Fibroblast Growth Factor, Type 1; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins