Glucose metabolism of malignant cells is not regulated by transketolase-like (TKTL)-1

Abstract

Abstract. An isoenzyme of transketolase, transketolase-like (TKTL)-1, has been hypothesized to play a pivotal role in the pathophysiology of malignant tumors. Available data are based on the detection of the putative TKTL-1 protein with one particular mouse monoclonal anti-TKTL-1 antibody, clone JFC12T10. In this study it was demonstrated that a) JFC12T10 detects multiple unspecific bands in Western blots, b) a 75-kDa band hitherto referred to as TKTL-1 corresponds to a nuclear protein and c) immunohistochemical detection of TKTL-1 in benign leiomyomas yields an expression pattern identical to that found in a variety of malignant tumors. In RT-PCR assays, using three different primer pairs for transketolase, TKTL-1 and yet another isogene of transketolase, TKTL-2, a relevant expression of TKTL-1 was not detectable in any of the 6 malignant tumor cell lines investigated (MCF-7, A549, HeLa, HT1080, M21 and TF-1). Expression levels of TKTL-1 were rather similar to those found for TKTL-2, although the latter has never been implicated in malignant disease. On the basis of these data, nutritional recommendations based on a hypothetically TKTL-1 controlled metabolism of tumor cells must be regarded as lacking scientific evidence.

Analysis and interpretation of transcriptomic data obtained from extended Warburg effect genes in patients with clear cell renal cell carcinoma

“…There is evidence that suggests that the role of TKTL1 may not be well understood. Mayer et al [ 159 ] used real-time PCR to investigate the presence of the TKTL1 gene in six different malignant cell lines and failed to find any evidence for the expression of this gene. In addition, they repeated the immunohistochemical studies using the same antibody used by the Langbein group [ 158 ] and reported staining of multiple unspecific bands in Western blots.…”

A Δ38 Deletion Variant of Human Transketolase as a Model of Transketolase-Like Protein 1 Exhibits No Enzymatic Activity

“…The authors did not provide any specific activities, but complete substrate turnover took as long as 24 hours under conditions, where substrates are completely depleted within a couple of minutes when using authentic human TKT [19]. In further challenge of the postulated role of TKTL1 in tumor cell metabolism, two recent studies could not confirm increased TKTL1 mRNA concentrations in different carcinomas and questioned the validity of the aforementioned immunohistochemical data 16,17. These results match our own observations (Schneider & Tittmann, unpublished) as we could not detect increased TKTL1 transcript levels in cell line HCT116 in contrast to data reported by others [12].…”

“…It has been hypothesized that TKTL1 could exhibit enzymatic activity that allows ATP synthesis in hypoxic and cancer cells in a pathway analogous to the phosphoketolase pathway present in some heterofermentative bacteria [12]. However, the presumed key role of TKTL1 in cancer cell metabolism has been put into question in numerous recent studies, where no overexpression of TKTL1 could be detected in several malignant tumor cell lines [16], [17].…”

TKTL1 expression in human malign and benign cell lines

“…Transketolase-like 1 (TKTL1) has gained increased attention due to several studies showing a TKTL1-positive staining of malignant tumor tissue of different origins [ 15 , 16 , 20 , 22 – 24 , 35 , 40 , 41 , 43 , 51 ] and its subsequent designation as a “proto-oncogene” [ 9 ]. Furthermore, several cancer cell lines have been reported to be positive for TKTL1 protein upon Western blot analysis [ 7 , 21 , 29 , 52 – 54 ], cyto-immunohistochemistry [ 50 , 55 ] and RT-qPCR. For example, Sun and coworkers analyzed TKTL1 expression in six HNSCC cell lines via Western blot with the JFC12T10 antibody and found that TKTL1 was relatively overexpressed in two cell lines (FaDU and UM22B) compared with levels in normal mucosal samples [ 29 ].…”