title: Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted.
abstract: Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactate-based matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.
authors.affiliation: Department of Urology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Langbein
authors.forename: M
authors.initials: M
authors.lastname: Zerilli
authors.forename: A
authors.initials: A
authors.lastname: Zur Hausen
authors.forename: W
authors.initials: W
authors.lastname: Staiger
authors.forename: K
authors.initials: K
authors.lastname: Rensch-Boschert
authors.forename: N
authors.initials: N
authors.lastname: Lukan
authors.forename: J
authors.initials: J
authors.lastname: Popa
authors.forename: M P
authors.initials: MP
authors.lastname: Ternullo
authors.forename: A
authors.initials: A
authors.lastname: Steidler
authors.forename: C
authors.initials: C
authors.lastname: Weiss
authors.forename: R
authors.initials: R
authors.lastname: Grobholz
authors.forename: F
authors.initials: F
authors.lastname: Willeke
authors.forename: P
authors.initials: P
authors.lastname: Alken
authors.forename: G
authors.initials: G
authors.lastname: Stassi
authors.forename: P
authors.initials: P
authors.lastname: Schubert
authors.forename: J F
authors.initials: JF
authors.lastname: Coy
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D006019:Glycolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D014174:Transketolase / Q000096:biosynthesis*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology
chemical_list: C505431:TKTL1 protein, human; D014174:Transketolase