Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification

Lim, Bo-Hyun; Cho, Bok-Im; Kim, Yu Na; Kim, Jae Won; Park, Soon-Tae; Lee, Chang-Won

doi:10.1038/emm.2006.54

Cited by 73 publications

(72 citation statements)

References 24 publications

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“…These results indicated that NNMT promoted EMT in gastric cancer cells mainly by upregulating TGF-β1 expression. It has been demonstrated that NNMT-mediated methylation is an important conjugation reaction in the biotransformation of a number of drugs and xenobiotics, including pyridine and other structurally-associated compounds (18). The epigenetic silencing of TGF-β1 genes is associated with the development of pituitary adenoma (33).…”

Section: Discussionmentioning

confidence: 99%

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Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

et al. 2018

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Abstract. Previous studies have demonstrated that nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in a number of tumors. In the present study, it was demonstrated that the gene and protein levels of NNMT were significantly increased in gastric cancer cells. Furthermore, upregulation of NNMT significantly increased the expression of mesenchymal markers, including α-smooth muscle actin (SMA), vimentin and fibronectin, but decreased the levels of epithelial cadherin. Since transforming growth factor (TGF)-β1 may serve a key function in epithelial-mesenchymal transition (EMT), the effects of NNMT on the expression of TGF-β1 were investigated in BGC-823 cells. The results demonstrated that overexpression of NNMT significantly induced the expression of TGF-β1. However, knockdown of NNMT inhibited the expression of TGF-β1, mothers against decapentaplegic homolog (Smad)2 and α-SMA. Additionally, pre-incubation with TGF-β1 partially eliminated NNMT-mediated changes in EMT. Collectively, the results demonstrated that upregulation of NNMT in gastric cancer cells may increase the expression of TGF-β1, therefore activating TGF-β1/Smad signaling, which in turn promotes EMT.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have also demonstrated that the upregulation of NNMT is associated with poor prognosis, advanced tumor stage, tumor cell migration and invasion (9,16,17). Although, overexpression of NNMT has been identified in gastric cancer (18), the underlying molecular mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

et al. 2018

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“…Balb/c mice were immunized three times at a 2-week interval, each time with 100 μg of purified recombinant mouse TMAP/CKAP2. On the fifth day after the final injection, cell fusion was performed with spleen cells and sp2/O-Ag14 myeloma cells as described by Lim et al (2006). Positive clones were selected by enzyme immunoassay.…”

Section: Production Of Monoclonal Antibodiesmentioning

confidence: 99%

Transient phosphorylation of tumor associated microtubule associated protein (TMAP)/cytoskeleton associated protein 2 (CKAP2) at Thr-596 during early phases of mitosis

et al. 2008

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Tumor associated microtubule associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2) is a mitotic spindle-associated protein whose expression is cell cycle-regulated and also frequently deregulated in cancer cells. Two monoclonal antibodies (mAbs) against TMAP/CKAP2 were produced: B-1-13 and D-12-3. Interestingly, the reactivity of mAb D-12-3 to TMAP/CKAP2 was markedly decreased specifically in mitotic cell lysate. The epitope mapping study showed that mAb D-12-3 recognizes the amino acid sequence between 569 and 625 and that phosphorylation at T596 completely abolishes the reactivity of the antibody, suggesting that the differential reactivity originates from the phosphorylation status at T596. Immunofluorescence staining showed that mAb D-12-3 fails to detect TMAP/CKAP2 in mitotic cells between prophase and metaphase, but the staining becomes evident again in anaphase, suggesting that phosphorylation at T596 occurs transiently during early phases of mitosis. These results suggest that the cellular functions of TMAP/CKAP2 might be regulated by timely phosphorylation and dephosphorylation during the course of mitosis.

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“…Isoelectric focusing, the first dimension of 2-DE was performed using a Multiphor II Electrophoresis System (Amersham Pharmacia, Uppsala, Sweden) as described in previous reports (Rabilloud, 1998;Choe and Lee, 2000;Gorg et al, 2000;Zuo and Speicher, 2000;Lim et al, 2006). IPG gel strips (Linear pH 4-7, 18 cm long) were rehydrated overnight (∼16 h) at room temperature in rehydration buffer (2 M thiourea, 7 M urea, 2% w/v CHAPS, 0.3% w/v DTT, 2% v/v IPG buffer and bromophenol blue).…”

Section: -De and Protein Identificationmentioning

confidence: 99%

Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model

et al. 2008

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Lung cancer is one of the deadliest and commonly diagnosed neoplasms. Early diagnosis of this disease is critical for improving clinical outcome and prognosis. Because the early stages of lung cancer often produce no symptoms, it is necessary to identify biomarkers for early detection, prognostic evaluation, and recurrence monitoring of the cancer. To identify potential lung cancer biomarkers, we analyzed the differential protein secretion from transformed bronchial epithelial cells (1198 and 1170-I) as compared to immortalized normal bronchial epithelial cells (BEAS-2B) and non-transformed cells (1799) all of which are derived from BEAS-2B and represent multistage bronchial epithelial carcinogenesis. The proteins recovered from the conditioned media of the cells were separated on two-dimensional gels. There was little difference between the secretome of the BEAS-2B and 1799 cells, whereas the patterns between the transformed 1198 and 1170-I cells and non-transformed 1799 cells were significantly different. Using mass spectrometry and database search, we identified 20 proteins including protein gene product 9.5 (PGP9.5), translationally controlled tumor protein (TCTP), tissue inhibitors of metalloproteinases-2 (TIMP-2), and triosephosphate isomerase (TPI), that were either increased or decreased simultaneously in conditioned media of both 1198 and 1170-I cells. Furthermore, levels of PGP9.5, TCTP, TIMP-2, and TPI were significantly increased not only in the conditioned media of both transformed cell lines when compared to those of BEAS-2B and 1799 cells, but also in plasmas and tissues from lung cancer patients when compared to those in normal controls. We suggest the PGP9.5, TCTP, TIMP-2, and TPI as promising candidates for lung cancer serum biomarkers.

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Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification

Cited by 73 publications

References 24 publications

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

Transient phosphorylation of tumor associated microtubule associated protein (TMAP)/cytoskeleton associated protein 2 (CKAP2) at Thr-596 during early phases of mitosis

Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model

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