TKTL1

Last updated
TKTL1
Identifiers
Aliases TKTL1 , TKR, TKT2, transketolase-like 1, transketolase like 1
External IDs OMIM: 300044 MGI: 1933244 HomoloGene: 8169 GeneCards: TKTL1
Orthologs
SpeciesHumanMouse
Entrez

8277

83553

Ensembl

ENSG00000007350

ENSMUSG00000031397

UniProt

P51854

Q99MX0

RefSeq (mRNA)

NM_012253
NM_001145933
NM_001145934

NM_031379

RefSeq (protein)

NP_001139405
NP_001139406
NP_036385

NP_113556

Location (UCSC) Chr X: 154.3 – 154.33 Mb Chr X: 73.22 – 73.25 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transketolase-like-1 (TKTL1) is a gene closely related to the transketolase gene (TKT). It emerged in mammals during the course of evolution and, according to the latest research findings, is considered one of the key genes that distinguishes modern humans (homo sapiens) from Neanderthals. [5] [6] [7]

Contents

The proteins formed by the two transketolase genes form a heterodimer (TKTL1-TKT). Once expressed, the TKTL1 protein displaces a TKT protein from the TKT-TKT homodimer, leading to the formation of a TKTL1-TKT heterodimer. This heterodimer is enzymatically very different from the transketolase homodimer (TKT-TKT), as the heterodimer leads to a significant increase in ribose-5-phosphate in cells. [8] TKTL1 also allows formation of acetyl-CoA, [9] an important component for the synthesis of lipids and steroids.

The TKTL1-Gene was discovered by Dr. Johannes Coy [10] and first published 1996. [5]

Function

The basic components ribose-5-phosphate and acetyl-CoA, which are formed by TKTL1, provide essential building blocks for the formation of new cells. TKTL1 controls the cell cycle and enables its execution by providing ribose, the building block necessary for DNA synthesis. [8] The production of ribose also provides the building block for DNA damage repair, so that activation of TKTL1 enables cancer cells to repair DNA damage induced by chemotherapy or radiotherapy more effectively and thus become resistant to these therapies. [11] [12] [13] [14]

TKTL1 also allows survival in the absence of oxygen (hypoxia). This protective program is triggered, for example, in the event of a ruptured blood vessel and a resulting oxygen deficiency. TKTL1 controls this hypoxia program, which allows cell survival in the absence of oxygen by fermenting glucose into lactic acid. [15] [16] The acid formed allows acid-based matrix degradation and tissue remodeling [17] as well as inhibition of immune cells that eliminate tumor cells. [18] [19] At the same time, TKTL1 and lactic acid control new blood vessel formation, which restores the supply of oxygen to healthy tissue or a tumor. [20] [21] [14]

The cell cycle is controlled differently than assumed. [8] The previous approach assumed that the consumption of ribose-5-phosphate, which begins with the initiation of the cell cycle, triggers a corresponding post-production so that the desired cell duplication can be accomplished (pull theory: "consumption pulls production").

TKTL1 is expressed first, followed by the formation of the heterodimer from TKTL1-TKT, which significantly increases the ribose-5-phosphate concentration, triggering the cell cycle. The TKTL1-mediated, increased ribose-5-phosphate concentration thus pushes the cell into the cell cycle (push effect).

On one hand, this metabolism forms the basis for new formation of healthy cells, however, on the other hand, it also leads to the new formation of undesired cells, such as cancer cells. TKTL1 plays a crucial role in the malignancy of cancer cells, regardless of the type of cancer. [22] Both the proliferation rate [23] and the ability to spread throughout the body and form metastases depend on TKTL1. [24] [23] and the ability to spread throughout the body and form metastases depend on TKTL1. [24] [25] Furthermore, TKTL1 also mediates protection of cancer cells from attack by the body's immune system, for example, by blocking killer cells via lactic acid formed (acid arrest), thus preventing them from reaching and killing cancer cells. [18] [19] In addition, TKTL1 also systematically suppresses the immune system, preventing tumors from being eliminated by the immune system. [26] [27]

TKTL1 has been shown to be involved in regulating neuronal development in the cerebral cortex. [28] A single nucleotide difference in the gene from archaic humans, including Neanderthals and Denisovans, and apes, is involved in neurodevelopment and may have resulted in humans possessing greater cognitive abilities. [29]

A Dresden research team led by Nobel Prize winner in medicine Svante Pääbo and Wieland B. Huttner were able to show in 2022 that modern humans produce more neurons in the frontal lobe during brain development than Neanderthals, caused by a change in a single amino acid found in the protein TKTL1. In Neanderthals, lysine is found there rather than arginine as in humans. Pääbo et al. thus answer the question of what makes modern humans unique compared to our closest relatives, the Neanderthals. [7] [30] [31]

When researching differences in gene expressions in the brains of domesticated and wild animals in 2012, Svante Pääbo also came across the TKTL1 gene. The researchers discovered that TKTL1 is the gene with the most significant difference in expression between domesticated dogs and wild wolves: activation of the gene is 47-fold higher in dogs than in wolves. [32]

Evolution

TKTL1 is a gene that arose from the transketolase gene of lower vertebrates by gene duplication in the course of vertebrate evolution and underwent crucial changes during their evolution. [33] It is found only in mammals. [34] In addition to the transketolase genes TKT and TKTL1, there is another member of the transketolase gene family in mammals, the TKTL2 gene. The TKTL2 gene arose by integration of a TKTL1 mRNA into the genome and thus, in contrast to the TKT and TKTL1 genes, has no introns. [34] Contrary to the TKT and TKTL1 genes, it is not yet clear in the case of the TKTL2 gene whether and what function TKTL2 performs. Compared to TKT and TKTL2, the TKTL1 protein has a deletion of 38 amino acids triggered by the non-use of the third exon. [33] This deletion of 38 amino acids also includes highly conserved and invariant amino acids that are present in all known transketolases. Due to the absence of these amino acids, which normally are always present in transketolases, the functionality of the TKTL1 protein was doubted for a long time. It was not until 2019 that a major breakthrough in deciphering the function of the TKTL1 gene was achieved by showing that the TKTL1 gene is able to displace a TKT protein from the TKT-TKT transketolase homodimer and form a TKTL1-TKT heterodimer that shows altered enzyme properties compared to the TKT-TKT homodimer. [8] Up to now, it is or was assumed that transketolases are enzymes that are active as homodimers. The detection of TKTL1-TKT heterodimers and the accompanying altered enzyme properties are of greatest importance to mammals because the altered enzyme properties trigger the formation of new cells by increasing the production of ribose, and thus significantly increasing the concentration of ribose in the cell. Since the sugar ribose and the deoxy-ribose formed from it are the crucial building block for DNA and RNA, the formation of the TKTL1-TKT heterodimer leads to the formation of the necessary sugar building block to create new DNA and RNA for the duplication of cells. TKTL1 controls the duplication of cells (cell cycle) and ensures that sufficient building blocks are present for cell duplication. [8] It was furthermore shown in 2021 that activation of transketolase is also used by viruses such as the SARS-CoV virus to influence the metabolism of the virus-infected cell in a manner that increases the production of the sugar building block ribose for new viruses, and thus viruses are produced more quickly and at a higher rate. [35] In addition to the formation of the sugar building block ribose, TKTL1 is able to form acetyl-CoA, another crucial building block for new cells. [9] Acetyl-CoA is the basic building block for the formation of energy-rich compounds such as fatty acids, ketone bodies or cholesterol. The TKTL1 enabled formation of acetyl-CoA represents a previously unknown pathway for the formation of acetyl-CoA. This pathway makes it possible to form acetyl-CoA even when acetyl-CoA formation, which runs via pyruvate dehydrogenase, is switched off. In contrast to pyruvate dehydrogenase-mediated acetyl-CoA formation, no decarboxylation is carried out with the help of TKTL1, so that the conversion of sugar to fat is possible without the loss of carbon atoms. This allows a cell to form acetyl-CoA much more effectively in order to form new cellular material such as cell membranes.

Detection methods

Currently, three lab methods exist for the detection of TKTL1. These are the direct determination of TKTL1 from blood, the immunohistochemical examination of tumor tissue for risk assessment, which is currently offered exclusively in the Bad Berka pathology department in Germany, and the measurement of TKTL1 in macrophages using EDIM technology, which is applied in the combined TKTL1 and DNaseX (Apo10) detection of PanTum Detect blood test.

Clinical significance

Cancer

TKTL1 protein was first detected in healthy cells and in tumor cells by immunohistochemistry in 2005. [34] Shortly thereafter, TKTL1 protein was shown to be increased in tumors compared to healthy tissue, and it identified patients with colorectal cancer and bladder cancer who showed faster mortality. [22] This study also discussed the role of TKTL1 in the fermentation of glucose to lactic acid despite the presence of oxygen, which was first described by Nobel Prize winner Otto Heinrich Warburg and which he termed "aerobic glycolysis". The coined term aerobic glycolysis used by Warburg, which he created to describe fermentation that was anaerobic but carried out under aerobic conditions, i.e., despite the presence of oxygen, led to great misunderstanding. In Warburg's honor, the fermentation of glucose to lactic acid was called the Warburg effect. In a 2006 study by Langbein et al., the Warburg effect was reinterpreted and the importance of this metabolic fermentation process for invasive destructive growth and metastasis of cancer cells was discussed. A subsequent study by Langbein demonstrated the role of TKTL1 and the switch of energy release to fermentation mediated by it in the metastasis of renal carcinomas, [36] identifying the clinical significance of TKTL1 expression in early tumor stages. The study was able to show that apparently quite benign tumors (stage T1) which led to the death of renal cancer patients after a short time were detected by TKTL1.

The clinical significance of TKTL1 as a marker in tumors for faster death (poor prognosis) of cancer patients has been demonstrated in a large number of studies. Studies in chronological order: 2006 – bladder and colon cancer, [22] 2007 – ovarian cancer, [37] 2009 – pediatric anaplastic nephroblastoma, [38] 2011 – rectal cancer, [11] 2011 – lung cancer, [25] 2012 – eye cancer, [39] 2013 – oral cavity carcinoma, [40] 2015 – esophageal cancer, [41] 2015 – gastric cancer, [42] 2018 – lung cancer, [43] 2019 – HPV infected cervix, [44] 2019 – ovarian cancer, [45] 2020 – colorectal cancer, [46] 2021 – liver cancer, [26] 2021 – colorectal cancer. [27]

Cancer diagnostics

Since all forms of cancer benefit from TKTL1-mediated malignancy factors, such as increased proliferation, oxygen-independent growth, invasiveness/metastasis and suppression of the immune system, detection of the TKTL1 protein affords the opportunity to detect cancer or premalignant lesions (precancerous lesions) using a blood sample.

In a study published in 2020 by the University of Tübingen, the detection of TKTL1 and another protein (DNaseX/Apo10) in blood scavenger cells was performed and it was shown that this can be used to detect colorectal cancer, bile duct cancer and pancreatic cancer very well and more effectively than with conventional test methods (tumor markers). [47]

In a study published in 2020 by the University of Tübingen, researchers detected TKTL1 and another protein (DNaseX/Apo10) in blood scavenger cells and were able to show that this can be used to detect colorectal cancer, bile duct cancer, and pancreatic cancer very well and more effectively than conventional test methods (tumor markers). [47]

A study conducted in 2022 under the auspices of the University Medical Center Eppendorf determined the proteins TKTL1 and DNaseX/Apo10 from blood in more than 5,000 subjects aged between 50 and 70 years who were considered healthy (Burg et al., 2022). In 82% of subjects with abnormal blood test results who were subsequently examined with imaging techniques such as MRI and PET/CT, symptomless cancer or precancerous lesions that had been undetected until the time of the study were found.

Studies at the University of Tübingen on the detection of cancer (rhabdomyosarcoma and neuroblastoma) in babies, children and young adults were able to show that the detection of TKTL1 and another protein (DNaseX/Apo10) in blood scavenger cells can provide very sensitive and specific evidence of the presence of these two types of cancer (Urla et al., 2022). [48]

Other diseases

The importance is currently being researched, including its association with:

Related Research Articles

<span class="mw-page-title-main">Aldolase A</span> Mammalian protein found in Homo sapiens

Aldolase A, also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ALDOA gene on chromosome 16.

<span class="mw-page-title-main">Transketolase</span> Enzyme involved in metabolic pathways

Transketolase is an enzyme that, in humans, is encoded by the TKT gene. It participates in both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis. Transketolase catalyzes two important reactions, which operate in opposite directions in these two pathways. In the first reaction of the non-oxidative pentose phosphate pathway, the cofactor thiamine diphosphate accepts a 2-carbon fragment from a 5-carbon ketose (D-xylulose-5-P), then transfers this fragment to a 5-carbon aldose (D-ribose-5-P) to form a 7-carbon ketose (sedoheptulose-7-P). The abstraction of two carbons from D-xylulose-5-P yields the 3-carbon aldose glyceraldehyde-3-P. In the Calvin cycle, transketolase catalyzes the reverse reaction, the conversion of sedoheptulose-7-P and glyceraldehyde-3-P to pentoses, the aldose D-ribose-5-P and the ketose D-xylulose-5-P.

<span class="mw-page-title-main">T-box transcription factor T</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.

<span class="mw-page-title-main">Tumor metabolome</span>

The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.

p16 Mammalian protein found in Homo sapiens

p16, is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer.

<span class="mw-page-title-main">Keratin 5</span>

Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.

<span class="mw-page-title-main">PARP1</span> Mammalian protein found in Homo sapiens

Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene. It is the most abundant of the PARP family of enzymes, accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus, but cytosolic fraction of this protein was also reported.

<span class="mw-page-title-main">Ribose-5-phosphate isomerase</span>

Ribose-5-phosphate isomerase (Rpi) encoded by the RPIA gene is an enzyme that catalyzes the conversion between ribose-5-phosphate (R5P) and ribulose-5-phosphate (Ru5P). It is a member of a larger class of isomerases which catalyze the interconversion of chemical isomers. It plays a vital role in biochemical metabolism in both the pentose phosphate pathway and the Calvin cycle. The systematic name of this enzyme class is D-ribose-5-phosphate aldose-ketose-isomerase.

<span class="mw-page-title-main">LPAR2</span> Protein-coding gene in the species Homo sapiens

Lysophosphatidic acid receptor 2 also known as LPA2 is a protein that in humans is encoded by the LPAR2 gene. LPA2 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

<span class="mw-page-title-main">PDK4</span> Protein-coding gene in the species Homo sapiens

Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial (PDK4) is an enzyme that in humans is encoded by the PDK4 gene. It codes for an isozyme of pyruvate dehydrogenase kinase.

<span class="mw-page-title-main">MSH3</span> Protein-coding gene in the species Homo sapiens

DNA mismatch repair protein, MutS Homolog 3 (MSH3) is a human homologue of the bacterial mismatch repair protein MutS that participates in the mismatch repair (MMR) system. MSH3 typically forms the heterodimer MutSβ with MSH2 in order to correct long insertion/deletion loops and base-base mispairs in microsatellites during DNA synthesis. Deficient capacity for MMR is found in approximately 15% of colorectal cancers, and somatic mutations in the MSH3 gene can be found in nearly 50% of MMR-deficient colorectal cancers.

<span class="mw-page-title-main">MTAP</span> Protein-coding gene in the species Homo sapiens

S-methyl-5'-thioadenosine phosphorylase (MTAP) is an enzyme in humans responsible for polyamine metabolism. It is encoded by the methylthioadenosine phosphorylase (MTAP) gene on chromosome 9. Multiple alternatively spliced transcript variants have been described for this gene, but their full-length natures remain unknown.

<span class="mw-page-title-main">DLC1</span> Protein-coding gene in the species Homo sapiens

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

<span class="mw-page-title-main">GALNT3</span> Protein-coding gene in the species Homo sapiens

Polypeptide N-acetylgalactosaminyltransferase 3 is an enzyme that in humans is encoded by the GALNT3 gene.

<span class="mw-page-title-main">ID4</span> Protein-coding gene in humans

ID4 is a protein coding gene. In humans, it encodes for the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.

<span class="mw-page-title-main">MGAT5</span> Protein-coding gene in the species Homo sapiens

Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A is an enzyme that in humans is encoded by the MGAT5 gene.

<span class="mw-page-title-main">Uroplakin-2</span>

Uroplakin-2 (UP2) is a protein that in humans is encoded by the UPK2 gene.

<span class="mw-page-title-main">Sodium-coupled monocarboxylate transporter 1</span> Protein-coding gene in the species Homo sapiens

Sodium-coupled monocarboxylate transporter 1 (i.e., SMCT1) and sodium-coupled monocarboxylate transporter 2 (i.e., SMCT2) are plasma membrane transport proteins in the solute carrier family. They transport sodium cations in association with the anionic forms (see conjugated base) of certain short-chain fatty acids (i.e., SC-FAs) through the plasma membrane from the outside to the inside of cells. For example, propionic acid (i.e., CH
3CH
2CO
2H) in its anionic "propionate" form (i.e., CH
3CH
2CO−
2) along with sodium cations (i.e., Na+) are co-transported from the extracellular fluid into a SMCT1-epxressing cell's cytoplasm. Monocarboxylate transporters (MCTs) are also transport proteins in the solute carrier family. They co-transport the anionic forms of various compounds into cells in association with proton cations (i.e. H+). Four of the 14 MCTs, i.e. SLC16A1 (i.e., MCT1), SLC16A7 (i.e., MCT22), SLC16A8 (i.e., MCT3), and SLC16A3 (i.e., MCT4), transport some of the same SC-FAs anions that the SMCTs transport into cells. SC-FAs do diffuse into cells independently of transport proteins but at the levels normally occurring in tissues far greater amounts of the SC-FAs are brought into cells that express a SC-FA transporter.

<span class="mw-page-title-main">Naa80</span> Protein-coding gene in the species Homo sapiens

N-acetyltransferase 80 is a protein that in humans is encoded by the NAA80 gene. It acetylates the N-terminus of mature actin.

Migration inducting gene 7 is a gene that corresponds to a cysteine-rich protein localized to the cell membrane and cytoplasm. It is the first-in-class of novel proteins translated from what are thought to be long Non-coding RNAs.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000007350 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031397 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Coy JF, Dübel S, Kioschis P, Thomas K, Micklem G, Delius H, Poustka A (March 1996). "Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes". Genomics. 32 (3): 309–316. doi:10.1006/geno.1996.0124. PMID   8838793.
  6. ↑ "TKTL1 transketolase-like 1". Entrez Gene. U.S. National Library of Medicine.
  7. 1 2 Pinson, Anneline; Xing, Lei; Namba, Takashi; Kalebic, Nereo; Peters, Jula; Oegema, Christina Eugster; Traikov, Sofia; Reppe, Katrin; Riesenberg, Stephan; Maricic, Tomislav; Derihaci, Razvan; Wimberger, Pauline; Pääbo, Svante; Huttner, Wieland B. (2022-09-09). "Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals" . Science. 377 (6611): eabl6422. doi:10.1126/science.abl6422. ISSN   0036-8075. PMID   36074851. S2CID   252161562.
  8. 1 2 3 4 5 Li Y, Yao CF, Xu FJ, Qu YY, Li JT, Lin Y, et al. (June 2019). "APC/CCDH1 synchronizes ribose-5-phosphate levels and DNA synthesis to cell cycle progression". Nature Communications. 10 (1): 2502. Bibcode:2019NatCo..10.2502L. doi:10.1038/s41467-019-10375-x. PMC   6555833 . PMID   31175280.
  9. 1 2 Diaz-Moralli S, Aguilar E, Marin S, Coy JF, Dewerchin M, Antoniewicz MR, et al. (August 2016). "A key role for transketolase-like 1 in tumor metabolic reprogramming". Oncotarget. 7 (32): 51875–51897. doi:10.18632/oncotarget.10429. PMC   5239521 . PMID   27391434.
  10. ↑ DE19527552C2,Poustka, Annemarie Dr&Coy, Johannes,"Transketolase-related protein",issued 1999-06-24
  11. 1 2 Schwaab J, Horisberger K, Ströbel P, Bohn B, Gencer D, Kähler G, et al. (August 2011). "Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy". BMC Cancer. 11: 363. doi: 10.1186/1471-2407-11-363 . PMC   3176245 . PMID   21854597.
  12. ↑ Dong Y, Wang M (January 2017). "Knockdown of TKTL1 additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells by regulating the levels of NADPH and ribose-5-phosphate". Biomedicine & Pharmacotherapy. 85: 672–678. doi:10.1016/j.biopha.2016.11.078. PMID   27916418.
  13. ↑ Zheng X, Li H (September 2018). "TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel". Biochemical and Biophysical Research Communications. 503 (2): 572–579. doi:10.1016/j.bbrc.2018.06.011. PMID   29885837. S2CID   47010679.
  14. 1 2 Heller S, Maurer GD, Wanka C, Hofmann U, Luger AL, Bruns I, et al. (July 2018). "Gene Suppression of Transketolase-Like Protein 1 (TKTL1) Sensitizes Glioma Cells to Hypoxia and Ionizing Radiation". International Journal of Molecular Sciences. 19 (8): E2168. doi: 10.3390/ijms19082168 . PMC   6121283 . PMID   30044385.
  15. ↑ Baptista I, Karakitsou E, Cazier JB, Günther UL, Marin S, Cascante M (March 2022). "TKTL1 Knockdown Impairs Hypoxia-Induced Glucose-6-phosphate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase Overexpression". International Journal of Molecular Sciences. 23 (7): 3574. doi: 10.3390/ijms23073574 . PMC   8999113 . PMID   35408935.
  16. ↑ Sun W, Liu Y, Glazer CA, Shao C, Bhan S, Demokan S, et al. (February 2010). "TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization". Clinical Cancer Research. 16 (3): 857–866. doi:10.1158/1078-0432.CCR-09-2604. PMC   2824550 . PMID   20103683.
  17. ↑ Stern R, Shuster S, Neudecker BA, Formby B (May 2002). "Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited". Experimental Cell Research. 276 (1): 24–31. doi:10.1006/excr.2002.5508. PMID   11978005.
  18. 1 2 Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, et al. (November 2016). "LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells". Cell Metabolism. 24 (5): 657–671. doi: 10.1016/j.cmet.2016.08.011 . PMID   27641098.
  19. 1 2 Wang JX, Choi SY, Niu X, Kang N, Xue H, Killam J, Wang Y (November 2020). "Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity". International Journal of Molecular Sciences. 21 (21): E8363. doi: 10.3390/ijms21218363 . PMC   7664620 . PMID   33171818.
  20. ↑ Dhup S, Dadhich RK, Porporato PE, Sonveaux P (2012). "Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis". Current Pharmaceutical Design. 18 (10): 1319–1330. doi:10.2174/138161212799504902. PMID   22360558. S2CID   388222.
  21. ↑ Lee DC, Sohn HA, Park ZY, Oh S, Kang YK, Lee KM, et al. (April 2015). "A lactate-induced response to hypoxia". Cell. 161 (3): 595–609. doi: 10.1016/j.cell.2015.03.011 . PMID   25892225. S2CID   14181524.
  22. 1 2 3 Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, et al. (February 2006). "Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted". British Journal of Cancer. 94 (4): 578–585. doi:10.1038/sj.bjc.6602962. PMC   2361175 . PMID   16465194.
  23. 1 2 Li J, Zhu SC, Li SG, Zhao Y, Xu JR, Song CY (August 2015). "TKTL1 promotes cell proliferation and metastasis in esophageal squamous cell carcinoma". Biomedicine & Pharmacotherapy. 74: 71–76. doi:10.1016/j.biopha.2015.07.004. PMID   26349965.
  24. 1 2 Xu X, Zur Hausen A, Coy JF, Löchelt M (March 2009). "Transketolase-like protein 1 (TKTL1) is required for rapid cell growth and full viability of human tumor cells". International Journal of Cancer. 124 (6): 1330–1337. doi:10.1002/ijc.24078. PMID   19065656. S2CID   20985253.
  25. 1 2 Kayser G, Sienel W, Kubitz B, Mattern D, Stickeler E, Passlick B, et al. (December 2011). "Poor outcome in primary non-small cell lung cancers is predicted by transketolase TKTL1 expression". Pathology. 43 (7): 719–724. doi:10.1097/PAT.0b013e32834c352b. PMID   22027741. S2CID   5510043.
  26. 1 2 Wang J, Li Y, Zhang C, Chen X, Zhu L, Luo T (September 2021). "A hypoxia-linked gene signature for prognosis prediction and evaluating the immune microenvironment in patients with hepatocellular carcinoma". Translational Cancer Research. 10 (9): 3979–3992. doi: 10.21037/tcr-21-741 . PMC   8798548 . PMID   35116696.
  27. 1 2 He X, Ding J, Cheng X, Xiong M (2021). "Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment and Predict the Prognosis of Colon Adenocarcinoma Patients". International Journal of General Medicine. 14: 9853–9862. doi: 10.2147/IJGM.S343216 . PMC   8687688 . PMID   34938106.
  28. ↑ Espinós A, Fernández-Ortuño E, Negri E, Borrell V (July 2022). "Evolution of genetic mechanisms regulating cortical neurogenesis". Developmental Neurobiology. 82 (5): 428–453. doi:10.1002/dneu.22891. PMC   9543202 . PMID   35670518. S2CID   249434041.
  29. ↑ Pinson A, Xing L, Namba T, Kalebic N, Peters J, Oegema CE, et al. (September 2022). "Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals". Science. 377 (6611): eabl6422. doi:10.1126/science.abl6422. PMID   36074851. S2CID   252161562.; Lay summary in: Zimmer C (8 September 2022). "What Makes Your Brain Different From a Neanderthal's?". The New York Times. Retrieved 10 September 2022.
  30. ↑ "Moderne Menschen bilden mehr Nervenzellen im Gehirn als Neandertaler". idw-online.de (in German). Retrieved 2022-11-14.
  31. ↑ Zeberg, Hugo; Jakobsson, Matthias; Pääbo, Svante (29 February 2024). "The genetic changes that shaped Neandertals, Denisovans, and modern humans". Cell. 187. doi:10.1016/j.cell.2023.12.029.
  32. ↑ Albert, Frank W.; Somel, Mehmet; Carneiro, Miguel; Aximu-Petri, Ayinuer; Halbwax, Michel; Thalmann, Olaf; Blanco-Aguiar, Jose A.; Plyusnina, Irina Z.; Trut, Lyudmila; Villafuerte, Rafael; Ferrand, Nuno; Kaiser, Sylvia; Jensen, Per; Pääbo, Svante (2012-09-27). "A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals". PLOS Genetics. 8 (9): e1002962. doi: 10.1371/journal.pgen.1002962 . ISSN   1553-7390. PMC   3459979 . PMID   23028369.
  33. 1 2 "TKTL1 - Schutzfaktor für Krebszellen und Tumormarker". Dr. Coy (in German). Retrieved 5 October 2022.
  34. 1 2 3 Coy JF, Dressler D, Wilde J, Schubert P (2005). "Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer". Clinical Laboratory. 51 (5–6): 257–273. PMID   15991799.
  35. ↑ Bojkova D, Costa R, Reus P, Bechtel M, Jaboreck MC, Olmer R, et al. (October 2021). "Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy". Metabolites. 11 (10): 699. doi: 10.3390/metabo11100699 . PMC   8540749 . PMID   34677415.
  36. ↑ Langbein S, Frederiks WM, zur Hausen A, Popa J, Lehmann J, Weiss C, et al. (June 2008). "Metastasis is promoted by a bioenergetic switch: new targets for progressive renal cell cancer". International Journal of Cancer. 122 (11): 2422–2428. doi: 10.1002/ijc.23403 . PMID   18302154. S2CID   1161404.
  37. ↑ Krockenberger M, Honig A, Rieger L, Coy JF, Sutterlin M, Kapp M, et al. (January 2007). "Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases". International Journal of Gynecological Cancer. 17 (1): 101–106. doi:10.1111/j.1525-1438.2007.00799.x. PMID   17291239. S2CID   23256394.
  38. ↑ Wu HT, Allie N, Myer L, Govender D (May 2009). "Anaplastic nephroblastomas express transketolase-like enzyme 1". Journal of Clinical Pathology. 62 (5): 460–463. doi:10.1136/jcp.2008.063966. PMID   19139037. S2CID   40815043.
  39. ↑ Lange CA, Tisch-Rottensteiner J, Böhringer D, Martin G, Schwartzkopff J, Auw-Haedrich C (September 2012). "Enhanced TKTL1 expression in malignant tumors of the ocular adnexa predicts clinical outcome". Ophthalmology. 119 (9): 1924–1929. doi:10.1016/j.ophtha.2012.03.037. PMID   22658715.
  40. ↑ Grimm M, Schmitt S, Teriete P, Biegner T, Stenzl A, Hennenlotter J, et al. (December 2013). "A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells". BMC Cancer. 13: 569. doi: 10.1186/1471-2407-13-569 . PMC   4235042 . PMID   24304513.
  41. ↑ Shi Z, Tang Y, Li K, Fan Q (November 2015). "TKTL1 expression and its downregulation is implicated in cell proliferation inhibition and cell cycle arrest in esophageal squamous cell carcinoma". Tumour Biology. 36 (11): 8519–8529. doi:10.1007/s13277-015-3608-7. PMID   26032094. S2CID   23723393.
  42. ↑ Song Y, Liu D, He G (2015). "TKTL1 and p63 are biomarkers for the poor prognosis of gastric cancer patients". Cancer Biomarkers. 15 (5): 591–597. doi:10.3233/CBM-150499. PMID   26406948.
  43. ↑ Millares L, Barreiro E, Cortes R, Martinez-Romero A, Balcells C, Cascante M, et al. (August 2018). "Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance". Lung Cancer. 122: 124–130. doi:10.1016/j.lungcan.2018.06.015. hdl: 10230/41739 . PMID   30032820.
  44. ↑ Chiarini A, Liu D, Rassu M, Armato U, Eccher C, Dal Prà I (2019). "Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients". Frontiers in Oncology. 9: 213. doi: 10.3389/fonc.2019.00213 . PMC   6456695 . PMID   31001477.
  45. ↑ Zhao M, Ye M, Zhou J, Zhu X (November 2019). "Prognostic values of transketolase family genes in ovarian cancer". Oncology Letters. 18 (5): 4845–4857. doi:10.3892/ol.2019.10818. PMC   6781755 . PMID   31611995.
  46. ↑ Peltonen R, Ahopelto K, Hagström J, Böckelman C, Haglund C, Isoniemi H (September 2020). "High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases". Cancer Biology & Therapy. 21 (9): 826–831. doi:10.1080/15384047.2020.1803008. PMC   7515493 . PMID   32795237.
  47. 1 2 Saman S, Stagno MJ, Warmann SW, Malek NP, Plentz RR, Schmid E (2020). "Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma". Cancer Biomarkers. 27 (1): 129–137. doi:10.3233/CBM-190414. PMC   7029314 . PMID   31771043.
  48. ↑ Stagno MJ, Schmidt A, Bochem J, Urla C, Handgretinger R, Cabanillas Stanchi KM, et al. (October 2022). "Epitope detection in monocytes (EDIM) for liquid biopsy including identification of GD2 in childhood neuroblastoma-a pilot study". British Journal of Cancer. 127 (7): 1324–1331. doi:10.1038/s41416-022-01855-x. PMC   9519569 . PMID   35864157.
  49. ↑ Li B, Iglesias-Pedraz JM, Chen LY, Yin F, Cadenas E, Reddy S, Comai L (April 2014). "Downregulation of the Werner syndrome protein induces a metabolic shift that compromises redox homeostasis and limits proliferation of cancer cells". Aging Cell. 13 (2): 367–378. doi:10.1111/acel.12181. PMC   3999508 . PMID   24757718.
  50. ↑ Rolland AD, Lavigne R, Dauly C, Calvel P, Kervarrec C, Freour T, et al. (January 2013). "Identification of genital tract markers in the human seminal plasma using an integrative genomics approach". Human Reproduction. 28 (1): 199–209. doi:10.1093/humrep/des360. PMID   23024119.
  51. ↑ Zeberg, Hugo; Jakobsson, Matthias; Pääbo, Svante (29 February 2024). "The genetic changes that shaped Neandertals, Denisovans, and modern humans". Cell. 187. doi:10.1016/j.cell.2023.12.029.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.