GLUT-1+/TKTL1+ coexpression predicts poor outcome in oral squamous cell carcinoma

Grimm, Martin; Munz, Adelheid; Teriete, Peter; Nadtotschi, Tatjana; Reinert, Siegmar

doi:10.1016/j.oooo.2014.02.007

Cited by 37 publications

(46 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cell culture, Western blot and densitometric quantification BICR3 and BICR56 OSCC cell lines [26,27] were cultured in DMEM F-12 medium (Invitrogen, Belgium) containing 10 % fetal calf serum (Sigma-Aldrich, Germany), 1 % fungicide, and penicillin/streptomycin (Biochrom, Germany) at 37°C and 5 % CO 2 .…”

Section: Staining Procedures and Quantification Of Immunohistochemistrymentioning

confidence: 99%

“…Our recent studies in OSCCs demonstrated glycolysis, glutaminolysis, and mitochondrial oxidative phosphorylation (OXPHOS) to play major roles in tumor metabolism [1,[4][5][6]. Moreover, the pentose phosphate pathway (PPP) [7] is a crucial factor for survival of OSCC tumor cells [8,9]. Intriguingly, the study conducted by Caneba et al [10] demonstrated that actually a higher mitochondrial activity measured by higher pyruvate uptake and oxygen consumption is related to increased ovarian cancer invasiveness.…”

Section: Introductionmentioning

confidence: 99%

“…TKT is a cytosolic enzyme and is regarded as a key player in the PPP, a major route for the biosynthesis of nucleotides [8,9]. Moreover, TKT-like 1 isoform TKTL1 has been shown to be responsible for generation of glutathione as an antioxidant of tumor cells (production of nicotinamide adenine dinucleotide phosphate, NADPH) linking the PPP with glutaminolysis and fatty acid synthesis [4,12,13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

Grimm¹,

Calgéer²,

Teriete

et al. 2015

Clin Transl Oncol

View full text Add to dashboard Cite

show abstract

Section: Staining Procedures and Quantification Of Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

Grimm¹,

Calgéer²,

Teriete

et al. 2015

Clin Transl Oncol

View full text Add to dashboard Cite

show abstract

“…11 In many other cancer forms too, such as colon, ocular, non-small cell lung cancer, and oral squamous cell cancer, TKTL1 overexpression predicts poor outcome. 4,7,[12][13][14] Colorectal cancer is the third most common cancer in men and the second most common in women globally. Some 1.4 million new cases are diagnosed annually, causing annually 694 000 deaths.…”

Section: Introductionmentioning

confidence: 99%

Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer

Ahopelto

Böckelman

Hagström

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

Background: Transketolase-like protein 1 (TKTL1) is an isoform of tranketolase, a key protein in a cancer cell's glucose metabolism that causes rapid cell growth and controls the non-oxidative part of the pentose phosphate pathway (PPP). Its overexpression occurs in several human cancer types. Our purpose was to study whether TKTL1 expression in colorectal cancer tissue associates with these patients' prognosis. Methods: We collected retrospectively patient data and tissue samples from 840 colorectal cancer patients treated at Helsinki University Hospital, then stained tumor tissue microarrays for TKTL1 by immunohistochemistry, and compared immunohistochemical tissue expression with clinicopathological parameters and survival. Results: High expression of TKTL1 associated with high Dukes stage, non-mucinous adenocarcinoma, and left-sided disease. Patients with high TKTL1 expression had poorer prognosis than those with low expression, with a 5-year disease-specific survival of 55.7% vs. 62.7%. Conclusion: We show that high TKTL1 in tumor tissue can lead to poor survival in colorectal cancer. TKTL1 thus can serve as a candidate marker for identifying patients at risk of recurrent disease.

show abstract

“…Tumor metabolism [5] with a special focus on increased hypoxia/glycolytic activity is regarded as a crucial factor for the carcinogenesis of OSCC and is associated with radio- and, chemotherapy resistance, as well as tumor recurrence [6-9]. …”

Section: Introductionmentioning

confidence: 99%

Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

Grimm¹,

Cetindis²,

Lehmann³

et al. 2014

J Transl Med

Self Cite

View full text Add to dashboard Cite

BackgroundTumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC).MethodsExpression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines.ResultsExpression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay).ConclusionsThis study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.

show abstract

GLUT-1+/TKTL1+ coexpression predicts poor outcome in oral squamous cell carcinoma

Cited by 37 publications

References 42 publications

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer

Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

Contact Info

Product

Resources

About