Increased expression of transketolase‐like‐1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph‐node metastases

Zerilli, M; Amato, Marco; Martorana, Annamaria; Cabibi, Daniela; Coy, Johannes F.; Cappello, Francesco; Pompei, G; Russo, Antonio; Giordano, Carla; Rodolico, Vito

doi:10.1002/cncr.23683

Cited by 37 publications

(25 citation statements)

References 36 publications

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“…According to the results of several clinical studies, overexpression of TKTL-1 is associated with a poor prognosis (2)(3)(4)(5). Experimental data have been published (1,(6)(7)(8) which apparently confirm the pathophysiological basis of TKTL-1-associated aggressiveness observed in clinical studies.…”

Section: Introductionsupporting

confidence: 59%

“…Omissions in this communication, however, prevent an objective evaluation of this interpretation. Nevertheless, several studies using the antibody clone JFC12T10 in other tumor entities also reported an unfavorable prognostic significance of increased expression of TKTL-1 (2,4,5). In the present study, the importance of TKTL-1 for malignant tumor cells has been evaluated on the basis of our own experimental data.…”

Section: Introductionmentioning

confidence: 93%

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

Mayer

Wallbrunn²,

Vaupel³

2010

Int J Oncol

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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.

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Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 93%

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

Mayer

Wallbrunn²,

Vaupel³

2010

Int J Oncol

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“…This is in accordance with a significant overexpression of TKTL1 in several different tumors like nasopharyngeal [16] , pulmonary [17] , thyroid papillary [18,19] , gastric [20] , ovarian [21,22] , cervical [23] and metastasizing renal cell carcinoma [11] . In general, increased TKTL1 expression correlates with poor patient outcome and tumor progression [20,[23][24][25] .…”

Section: Introductionmentioning

confidence: 48%

Hypoxia Induces the Expression of Transketolase-Like 1 in Human Colorectal Cancer

Bentz¹,

Cee²,

Endlicher

et al. 2013

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Background and Aims: Transketolase-like (TKTL) 1 is one of the key enzymes for anaerobic sugar degradation even in the presence of oxygen (aerobic glycolysis). Transketolase-dependent reactions supply malignant tumors with ribose and NADPH. Therefore, TKTL1 activity could be crucial for tumor proliferation and survival. The aim of the study was to evaluate the expression of TKTL1 in colorectal cancer (CRC) and its regulation under hypoxic conditions. Methods: We studied TKTL1 mRNA and protein expression in CRC cell lines and human CRC biopsies by quantitative real-time PCR, Western blotting and immunohistochemistry. Regulation of TKTL1 under oxygen depletion was analyzed by cultivating cells either in a three-dimensional spheroid model or in a hypoxia incubator chamber. Results: TKTL1 mRNA was heterogeneously expressed in monolayers of cells with high levels in HT-29 and SW480. TKTL1 protein was also clearly detectable in HT-29 and SW480. Hypoxia-inducible factor (HIF)-1 protein expression correlated with TKTL1 protein expression in SW480 spheroids over time. On the one hand, induction of hypoxia in T84 spheroids did not induce TKTL1; on the other hand, hypoxia by incubation at 1% O2 in a hypoxia incubator chamber clearly showed an upregulation of TKTL1. In 50% of CRC patients, TKTL1 protein expression was upregulated in tumor compared to non-tumor tissue. The immunohistochemical staining of TKTL1 in CRC patient samples resulted in 14 positive and 30 negative samples. Conclusions: TKTL1 expression correlated with HIF-1 protein expression and was induced upon hypoxic conditions which could facilitate energy supply to tumors under these circumstances. © 2013 S. Karger AG, Basel.

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“…Via genome duplication and exon skipping, higher vertebrates acquired transketolase-like 1 (TKTL1), which compared to TKT protein lacks 38 amino acid residues [8, 9]. TKTL1 is upregulated in various cancer cells and tissues [4, 5, 10–13], and TKTL1 overexpression in cancer patients is correlated with malignancy, invasiveness, therapeutic resistance and poor prognosis [11, 14–16]. TKTL1 is required for rapid growth and viability of tumor cells [17], and protects against apoptosis induced by growth factor withdrawal [18], oxidative stress [17–19], cytotoxic therapy or targeted therapies [16, 20], while TKTL1 silencing hinders cancer cell proliferation [17, 21].…”

Section: Introductionmentioning

confidence: 99%

A key role for transketolase-like 1 in tumor metabolic reprogramming

et al. 2016

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Metabolic reprogramming, a crucial cancer hallmark, shifts metabolic pathways such as glycolysis, tricarboxylic acid cycle or lipogenesis, to enable the growth characteristics of cancer cells. Here, we provide evidence that transketolase-like 1 (TKTL1) orchestrates aerobic glycolysis, fatty acid and nucleic acid synthesis, glutamine metabolism, protection against oxidative stress and cell proliferation. Furthermore, silencing of TKTL1 reduced the levels of sphingolipids such as lactosylceramide (a sphingolipid regulating cell survival, proliferation and angiogenesis) and phosphatidylinositol (which activates PI3K/Akt/mTOR signaling). Thus, in addition to its well-known roles in glucose and amino acid metabolism, TKTL1 also regulates lipid metabolism. In conclusion, our study provides unprecedented evidence that TKTL1 plays central roles in major metabolic processes subject to reprogramming in cancer cells and thus identifies TKTL1 as a promising target for new anti-cancer therapies.

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Increased expression of transketolase‐like‐1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph‐node metastases

Cited by 37 publications

References 36 publications

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

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

Hypoxia Induces the Expression of Transketolase-Like 1 in Human Colorectal Cancer

A key role for transketolase-like 1 in tumor metabolic reprogramming

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