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ASCT2

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https://www.readbyqxmd.com/read/29221178/cytotoxic-stress-induces-transfer-of-mitochondria-associated-human-endogenous-retroviral-rna-and-proteins-between-cancer-cells
#1
David Díaz-Carballo, Jacqueline Klein, Ali H Acikelli, Camilla Wilk, Sahitya Saka, Holger Jastrow, Gunther Wennemuth, Phillip Dammann, Urs Giger-Pabst, Veria Khosrawipour, Joachim Rassow, Mikalai Nienen, Dirk Strumberg
About 8 % of the human genome consists of human endogenous retroviruses (HERVs), which are relicts of ancient exogenous retroviral infections incurred during evolution. Although the majority of HERVs have functional gene defects or epigenetic modifications, many of them are still able to produce retroviral proteins that have been proposed to be involved in cellular transformation and cancer development. We found that, in chemo-resistant U87RETO glioblastoma cells, cytotoxic stress induced by etoposide promotes accumulation and large-scale fission of mitochondria, associated with the detection of HERV-WE1 (syncytin-1) and HERV-FRD1 (syncytin-2) in these organelles...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29202102/combinatorial-treatment-with-natural-compounds-in-prostate-cancer-inhibits-prostate-tumor-growth-and-leads-to-key-modulations-of-cancer-cell-metabolism
#2
Alessia Lodi, Achinto Saha, Xiyuan Lu, Bo Wang, Enrique Sentandreu, Meghan Collins, Mikhail G Kolonin, John DiGiovanni, Stefano Tiziani
High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism...
2017: NPJ Precision Oncology
https://www.readbyqxmd.com/read/29151270/asct2-defined-by-enzyme-mediated-activation-of-radical-sources-enhances-malignancy-of-gd2-plus-small-cell-lung-cancer
#3
Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa
Ganglioside GD2 is specifically expressed in small cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we performed enzyme-mediated activation of radical sources combined with mass spectrometry in GD2 positive (+) SCLC cells. Consequently, we identified ASC amino-acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2...
November 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/29020998/proteomic-profiling-of-breast-cancer-metabolism-identifies-shmt2-and-asct2-as-prognostic-factors
#4
Stephan Bernhardt, Michaela Bayerlová, Martina Vetter, Astrid Wachter, Devina Mitra, Volker Hanf, Tilmann Lantzsch, Christoph Uleer, Susanne Peschel, Jutta John, Jörg Buchmann, Edith Weigert, Karl-Friedrich Bürrig, Christoph Thomssen, Ulrike Korf, Tim Beissbarth, Stefan Wiemann, Eva Johanna Kantelhardt
BACKGROUND: Breast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, are less well-understood. Profiling of metabolism-related proteins harbors the potential to establish new patient stratification regimes and biomarkers promoting individualized therapy. In our study, we aimed to examine the relationship between metabolism-associated protein expression profiles and clinicopathological characteristics in a large cohort of breast cancer patients...
October 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28885889/a-genetic-variant-of-asct2-hampers-in-vitro-rna-splicing-and-correlates-with-human-longevity
#5
Patrizia D'Aquila, Paolina Crocco, Francesco De Rango, Cesare Indiveri, Dina Bellizzi, Giuseppina Rose, Giuseppe Passarino
Given the role of amino acid regulation for physiological and pathological cell proliferation, we investigated whether the variability of solute carrier family 1, member 5 (SLC1A5, namely ASCT2), encoding for ASCT2 protein, a major glutamine transporter, is related to longevity. A total of 607 differently aged unrelated individuals, 351 very old subjects (≥85 years, range 85-106 years, mean age 93.82 ± 4.44 years) and 256 younger controls (<85 years, range 64-84 years, mean age 73.60 ± 5.70 years) were analyzed...
September 8, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28807674/phenylglycine-analogs-are-inhibitors-of-the-neutral-amino-acid-transporters-asct1-and-asct2-and-enhance-nmda-receptor-mediated-ltp-in-rat-visual-cortex-slices
#6
Alan C Foster, Natalie Rangel-Diaz, Ursula Staubli, Jia-Ying Yang, Mahmud Penjwini, Veena Viswanath, Yong-Xin Li
The N-methyl-d-aspartate receptor (NMDA) co-agonist d-serine is a substrate for the neutral amino acid transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). We identified l-phenylglycine (PG) and its analogs as inhibitors of ASCT1 and ASCT2. PG analogs were shown to be non-substrate inhibitors of ASCT1 and ASCT2 with a range of activities relative to other amino acid transport systems, including sodium-dependent glutamate transporters, the sodium-independent d-serine transporter asc-1 and system L. L-4-chloroPG was the most potent and selective ASCT1/2 inhibitor identified...
August 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28804556/anti-tumor-efficacy-evaluation-of-a-novel-monoclonal-antibody-targeting-neutral-amino-acid-transporter-asct2-using-patient-derived-xenograft-mouse-models-of-gastric-cancer
#7
Noriyuki Kasai, Aya Sasakawa, Kenta Hosomi, Tze Wei Poh, Bernadette Lynn Chua, Wei Peng Yong, Jimmy So, Shing Leng Chan, Richie Soong, Koji Kono, Toshihiko Ishii, Kazuya Yamano
ASC amino acid transporter 2 (ASCT2), also known as solute linked carrier family 1 member A5 (SLC1A5) is a Na+-dependent glutamine/neutral amino acid transporter. ASCT2 acts as a high-affinity transporter of L-glutamine (Gln) and has been reported to be up-regulated in a variety of cancerous tissues including stomach, liver, and kidney. In this study, we evaluated anti-tumor efficacy of a novel anti-ASCT2 humanized monoclonal antibody, KM8094, which has a neutralizing activity against glutamine uptake, as a therapeutic antibody against gastric cancer and explored clinical predictive biomarker candidates by utilizing patient-derived xenograft (PDX) mouse models...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28759021/asct2-regulates-glutamine-uptake-and-cell-growth-in-endometrial-carcinoma
#8
A D Marshall, M van Geldermalsen, N J Otte, T Lum, M Vellozzi, A Thoeng, A Pang, R Nagarajah, B Zhang, Q Wang, L Anderson, J E J Rasko, J Holst
Glutamine commonly becomes a conditionally essential amino acid in cancer. Glutamine is supplied to the cell by transporters such as ASCT2 (SLC1A5), which is frequently upregulated in multiple cancers. Here we investigated the expression of ASCT2 in endometrial carcinoma, and evaluated the contribution of ASCT2 to glutamine uptake and endometrial cancer cell growth. Analysis of human gene expression data showed that ASCT2 was significantly upregulated in both endometrioid and serous subtypes of endometrial carcinoma, compared to normal, age-matched endometrium...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28749408/clinical-role-of-asct2-slc1a5-in-kras-mutated-colorectal-cancer
#9
Kosuke Toda, Gen Nishikawa, Masayoshi Iwamoto, Yoshiro Itatani, Ryo Takahashi, Yoshiharu Sakai, Kenji Kawada
Mutation in the KRAS gene induces prominent metabolic changes. We have recently reported that KRAS mutations in colorectal cancer (CRC) cause alterations in amino acid metabolism. However, it remains to be investigated which amino acid transporter can be regulated by mutated KRAS in CRC. Here, we performed a screening of amino acid transporters using quantitative reverse-transcription polymerase chain reaction (RT-PCR) and then identified that ASCT2 (SLC1A5) was up-regulated through KRAS signaling. Next, immunohistochemical analysis of 93 primary CRC specimens revealed that there was a significant correlation between KRAS mutational status and ASCT2 expression...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28729677/engineering-tumour-cell-binding-synthetic-polymers-with-sensing-dense-transporters-associated-with-aberrant-glutamine-metabolism
#10
Naoki Yamada, Yuto Honda, Hiroyasu Takemoto, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Masamitsu Konno, Hideshi Ishii, Masaki Mori, Nobuhiro Nishiyama
Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a selective high affinity to tumour cells overexpressing glutaminolysis-related transporter ASCT2. In in vitro study, our developed polymer exhibited faster and higher cellular uptake in tumour cells than that in normal cells...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692032/epigenetic-silencing-of-microrna-137-enhances-asct2-expression-and-tumor-glutamine-metabolism
#11
J Dong, D Xiao, Z Zhao, P Ren, C Li, Y Hu, J Shi, H Su, L Wang, H Liu, B Li, P Gao, G Qing
Tumor cells must activate specific transporters to meet their increased glutamine metabolic demands. Relative to other glutamine transporters, the ASC family transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide spectrum of human cancers to coordinate metabolic reprogramming and malignant transformation. Understanding the molecular mechanisms whereby tumor cells frequently upregulate this transporter is therefore vital to develop potential strategies for transporter-targeted therapies. Combining in-silico algorithms with systemic experimental screening, we herein identify the tumor suppressor microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell glutamine metabolism...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28625135/studying-interactions-of-drugs-with-cell-membrane-nutrient-transporters-new-frontiers-of-proteoliposome-nanotechnology
#12
Mariafrancesca Scalise, Michele Galluccio, Lorena Pochini, Lara Console, Maria Barile, Nicola Giangregorio, Annamaria Tonazzi, Cesare Indiveri
Transport systems are hydrophobic proteins localized in cell membranes where they mediate transmembrane flow of nutrients, ions and any other compounds essential for cell metabolism. More than 400 transporters of the SoLuteCarrier (SLC) group are present in human cells. Transporters take contacts also with xenobiotics, thus mediating absorption and/or interaction with these exogenous compounds. Since drugs belong to xenobiotics, transporters gained interest also in drug discovery. Transporters differentially expressed in pathological conditions are exploited as drug targets...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28623466/increases-in-circulating-amino-acids-with-in-feed-antibiotics-correlated-with-gene-expression-of-intestinal-amino-acid-transporters-in-piglets
#13
Miao Yu, Chunlong Mu, Yuxiang Yang, Chuanjian Zhang, Yong Su, Zan Huang, Kaifan Yu, Weiyun Zhu
In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic...
June 16, 2017: Amino Acids
https://www.readbyqxmd.com/read/28553292/asct2-slc1a5-deficient-mice-have-normal-b-cell-development-proliferation-and-antibody-production
#14
Etienne Masle-Farquhar, Angelika Bröer, Mehmet Yabas, Anselm Enders, Stefan Bröer
SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5's primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28536503/epigenetic-activation-of-asct2-in-the-hippocampus-contributes-to-depression-like-behavior-by-regulating-d-serine-in-mice
#15
Jiesi Wang, Ke Zhang, Xiaojuan Chen, Xiaoqian Liu, Huajing Teng, Mei Zhao, Zhongsheng Sun
The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na(+)-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS) in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28516268/gpna-inhibits-the-sodium-independent-transport-system-l-for-neutral-amino-acids
#16
Martina Chiu, Cosimo Sabino, Giuseppe Taurino, Massimiliano G Bianchi, Roberta Andreoli, Nicola Giuliani, Ovidio Bussolati
L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. The kinetics of the effect suggests that GPNA is a low affinity, competitive inhibitor of system L transporters. In Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but not ASCT2 silencing, lowers the cell content of leucine...
May 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28440528/-effect-of-asct2-gene-knock-down-by-shrna-on-biological-behaviors-of-colorectal-cancer-cells
#17
Canfeng Cai, Bing Zeng, Jun Zeng, Haiyang Xin, Chaoming Tang
OBJECTIVE: To investigate the effect of ASCT2 gene (glutamine transporter) knock-down by shRNA on biological behaviors of colorectal cancer cells. METHODS: shRNA was transfected into colorectal cancer cells Lovo and SW480 to knockdown ASCT2 mediated by Lipofectamine 2000. Reverse transcription-PCR and Western blot were used to examine the mRNA and protein expression of ASCT2. MTT and transwell assay were used to determine the proliferation and invasiveness of Lovo and SW480 cells...
April 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28252650/amino-acid-transporters-in-t-cell-activation-and-differentiation
#18
REVIEW
W Ren, G Liu, J Yin, B Tan, G Wu, F W Bazer, Y Peng, Y Yin
T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 (l-leucine transporter), ASCT2 (l-glutamine transporter) and GAT-1 (γ-aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28174119/potential-transfer-of-neurotoxic-amino-acid-%C3%AE-n-methylamino-alanine-bmaa-from-mother-to-infant-during-breast-feeding-predictions-from-human-cell-lines
#19
Marie Andersson, Lisa Ersson, Ingvar Brandt, Ulrika Bergström
β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [(14)C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [(14)C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans...
April 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28112360/low-uptake-of-fluorodeoxyglucose-in-positron-emission-tomography-computed-tomography-in-ovarian-clear-cell-carcinoma-may-reflect-glutaminolysis-of-its-cancer-stem-cell-like-properties
#20
Masakazu Sato, Kei Kawana, Katsuyuki Adachi, Asaha Fujimoto, Ayumi Taguchi, Tomona Fujikawa, Mitsuyo Yoshida, Hiroe Nakamura, Haruka Nishida, Tomoko Inoue, Juri Ogishima, Satoko Eguchi, Aki Yamashita, Kensuke Tomio, Takahide Arimoto, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Yutaka Osuga, Tomoyuki Fujii
The characteristics of ovarian cancers that showed low activation of glycolysis were investigated. Using medical records of patients with ovarian cancers who had undergone fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) prior to their primary surgery at the University of Tokyo Hospital between 2010 and 2015, we identified cases with a low uptake of FDG in PET/CT. We considered the maximum standardized uptake value (SUVmax) as the degree of glucose uptake. We investigated the properties which may account for the low activation of glycolysis in vitro...
March 2017: Oncology Reports
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