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EMT metabolism

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https://www.readbyqxmd.com/read/28525556/transcriptome-of-the-gsh-depleted-lens-reveals-changes-in-detoxification-and-emt-signaling-genes-transport-systems-and-lipid-homeostasis
#1
Jeremy A Whitson, Xiang Zhang, Mario Medvedovic, Jenny Chen, Zongbo Wei, Vincent M Monnier, Xingjun Fan
Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28514740/differential-expression-of-circulating-biomarkers-of-tumor-phenotype-and-outcomes-in-previously-treated-non-small-cell-lung-cancer-patients-receiving-erlotinib-vs-cytotoxic-chemotherapy
#2
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499590/mir-93-5p-inhibits-the-emt-of-breast-cancer-cells-via-targeting-mkl-1-and-stat3
#3
Yuan Xiang, Xing-Hua Liao, Cheng-Xi Yu, Ao Yao, Huan Qin, Jia-Peng Li, Peng Hu, Hui Li, Wei Guo, Chao-Jiang Gu, Tong-Cun Zhang
Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and Signal transducer and activator of transcription 3 (STAT3) have been implicated in the control of cellular metabolism, survival and growth. Our previous study has shown that cooperativity of MKL-1 and STAT3 promoted breast cancer cell migration. Herein, we demonstrate a requirement for MKL-1 and STAT3 in miRNA-mediated cellular EMT to affect breast cancer cell migration...
May 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28489600/oleate-induced-ptx3-promotes-head-and-neck-squamous-cell-carcinoma-metastasis-through-the-up-regulation-of-vimentin
#4
Shih-Hung Chan, Jhih-Peng Tsai, Chih-Jie Shen, Yu-Han Liao, Ben-Kuen Chen
The association between metabolic diseases and the risk of developing cancer is emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia-associated tumor metastasis remains unknown. In this study, we found that oleate induced PTX3 expression and secretion through the activation of Akt/NF-κB pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF-κB was essential for the oleate-induced stabilization of PTX3 mRNA. In addition, both the depletion of PTX3 and the inhibition of NF-κB significantly inhibited oleate-induced tumor cell migration and invasion...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444969/metabolic-reprogramming-and-epithelial-to-mesenchymal-transition-in-cancer
#5
REVIEW
Marco Sciacovelli, Christian Frezza
Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelial-to-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions...
April 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28438397/endothelial-to-mesenchymal-transition-a-novel-therapeutic-target-for-cardiovascular-diseases
#6
REVIEW
Ampadu O Jackson, Jingjing Zhang, Zhisheng Jiang, Kai Yin
Endothelial-to-mesenchymal transition (EndMT) is a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype. Similar to epithelial-to-mesenchymal transition (EMT), EndMT can be induced by multiple stimulants such as cytokines and metabolic factors that play crucial roles in the development of the cardiovascular system. Recent studies have demonstrated that EndMT may play a significant role in the pathogenesis of cardiovascular diseases (CVDs), and may represent a novel therapeutic target for cardiovascular remodeling and fibrotic disorders...
March 16, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28435451/ahnak2-is-a-novel-prognostic-marker-and-oncogenic-protein-for-clear-cell-renal-cell-carcinoma
#7
Minglei Wang, Xuefeng Li, Jin Zhang, Qiong Yang, Wenqi Chen, Weilin Jin, Yi-Ran Huang, Ru Yang, Wei-Qiang Gao
Integrative database analysis was performed to identify novel candidate oncogene AHNAK2 overexpressed in clear cell renal cell carcinoma (ccRCC). However, the function of AHNAK2 in cancer cells is currently unknown. In this study, we first confirmed the upregulation of AHNAK2 in ccRCC tissues compared with adjacent normal tissues in 15 pairs of samples. Then we analyzed AHNAK2 expression in a large cohort of ccRCC patient samples (n = 355), and found that up-regulation of AHNAK2 was positively correlated with tumor progression and poor survival (p = 0...
2017: Theranostics
https://www.readbyqxmd.com/read/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#8
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28414315/the-emt-activator-zeb1-is-a-key-factor-for-cell-plasticity-and-promotes-metastasis-in-pancreatic-cancer
#9
Angela M Krebs, Julia Mitschke, María Lasierra Losada, Otto Schmalhofer, Melanie Boerries, Hauke Busch, Martin Boettcher, Dimitrios Mougiakakos, Wilfried Reichardt, Peter Bronsert, Valerie G Brunton, Christian Pilarsky, Thomas H Winkler, Simone Brabletz, Marc P Stemmler, Thomas Brabletz
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28413640/clinicopathological-examination-of-dipeptidase-1-expression-in-colorectal-cancer
#10
Kazunoshin Tachibana, Motonobu Saito, Jun-Ichi Imai, Emi Ito, Yuka Yanagisawa, Reiko Honma, Katsuharu Saito, Jin Ando, Tomoyuki Momma, Shinji Ohki, Tohru Ohtake, Shinya Watanabe, Satoshi Waguri, Seiichi Takenoshita
Dipeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is fundamental in glutathione and leukotriene metabolism. DPEP1 was initially considered as a tumor suppressor gene in Wilms' tumor and breast cancer. However, it has been reported that DPEP1 is upregulated in colorectal cancers (CRCs) and high DPEP1 expression levels are associated with poorer patient survival. The role of DPEP1 genes in CRC, as well as their expression, requires investigation. Therefore, the present study investigated DPEP1 expression using reverse transcription-quantitative polymerase chain reaction or immunohistochemistry on surgically resected samples from CRC cases, and further examined the biological significance of DPEP1 by comparing the expression of the epithelial to mesenchymal transition (EMT) markers, including epithelial cadherin and Vimentin to clarify the function of DPEP1 in CRC, particularly in metastasis...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28406185/knockdown-of-stem-cell-regulator-oct4a-in-ovarian-cancer-reveals-cellular-reprogramming-associated-with-key-regulators-of-cytoskeleton-extracellular-matrix-remodelling
#11
Chantel Samardzija, David W Greening, Ruth Escalona, Maoshan Chen, Maree Bilandzic, Rodney Luwor, George Kannourakis, Jock K Findlay, Nuzhat Ahmed
Oct4A is a master regulator of self-renewal and pluripotency in embryonic stem cells. It is a well-established marker for cancer stem cell (CSC) in malignancies. Recently, using a loss of function studies, we have demonstrated key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in vitro and in vivo models of ovarian cancer. In an effort to understand the regulatory role of Oct4A in tumor biology, we employed the use of an ovarian cancer shRNA Oct4A knockdown cell line (HEY Oct4A KD) and a global mass spectrometry (MS)-based proteomic analysis to investigate novel biological targets of Oct4A in HEY samples (cell lysates, secretomes and mouse tumor xenografts)...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393186/a-novel-5-fluorouracil-resistant-human-esophageal-squamous-cell-carcinoma-cell-line-eca-109-5-fu-with-significant-drug-resistance-related-characteristics
#12
Chi Zhang, Qunfeng Ma, Yinan Shi, Xue Li, Ming Wang, Junfeng Wang, Jianlin Ge, Zhinan Chen, Ziling Wang, Hong Jiang
5-Fluorouracil (5-FU) is used for the clinical treatment of esophageal squamous cell carcinomas (ESCCs), yet it also induces chemoresistant cancer cells during treatment, which leads to the failure of the therapy. To further explore the resistance mechanism of 5-FU in ESCC, we established the 5-FU-resistant ESCC cell line Eca-109/5-FU, which was prepared by the stepwise exposure to increasing 5-FU concentrations. MTT assay and nude mouse xenograft models were used to test the drug resistance and proliferation of Eca-109 and Eca-109/5-FU cells in vitro and in vivo...
March 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28362858/3-bromopyruvate-and-buthionine-sulfoximine-effectively-kill-anoikis-resistant-hepatocellular-carcinoma-cells
#13
Minjong Lee, Ara Jo, Seulki Lee, Jong Bin Kim, Young Chang, Joon Yeul Nam, Hyeki Cho, Young Youn Cho, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
BACKGROUND & AIMS: Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells. METHODS: We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells...
2017: PloS One
https://www.readbyqxmd.com/read/28352611/targeting-the-metabolic-reprogramming-that-controls-epithelial-to-mesenchymal-transition-in-aggressive-tumors
#14
REVIEW
Andrea Morandi, Maria Letizia Taddei, Paola Chiarugi, Elisa Giannoni
The epithelial-to-mesenchymal transition (EMT) process allows the trans-differentiation of a cell with epithelial features into a cell with mesenchymal characteristics. This process has been reported to be a key priming event for tumor development and therefore EMT activation is now considered an established trait of malignancy. The transcriptional and epigenetic reprogramming that governs EMT has been extensively characterized and reviewed in the last decade. However, increasing evidence demonstrates a correlation between metabolic reprogramming and EMT execution...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28345629/wt1-expression-in-breast-cancer-disrupts-the-epithelial-mesenchymal-balance-of-tumour-cells-and-correlates-with-the-metabolic-response-to-docetaxel
#15
Mara Artibani, Andrew H Sims, Joan Slight, Stuart Aitken, Anna Thornburn, Morwenna Muir, Valerie G Brunton, Jorge Del-Pozo, Linda R Morrison, Elad Katz, Nicholas D Hastie, Peter Hohenstein
WT1 is a transcription factor which regulates the epithelial-mesenchymal balance during embryonic development and, if mutated, can lead to the formation of Wilms' tumour, the most common paediatric kidney cancer. Its expression has also been reported in several adult tumour types, including breast cancer, and usually correlates with poor outcome. However, published data is inconsistent and the role of WT1 in this malignancy remains unclear. Here we provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342867/gsk3%C3%AE-attenuates-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-and-metabolic-alterations-in-arpe-19-cells
#16
Li Huang, Cheng Zhang, Li Su, Zhengyu Song
While TGF-β1 is known to induce epithelial-mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28337746/thymidylate-synthase-is-functionally-associated-with-zeb1-and-contributes-to-the-epithelial-to-mesenchymal-transition-of-cancer-cells
#17
Aarif Siddiqui, Maria Eleni Vazakidou, Annemarie Schwab, Francesca Napoli, Cristina Fernandez-Molina, Ida Rapa, Marc P Stemmler, Marco Volante, Thomas Brabletz, Paolo Ceppi
Thymidylate synthase (TS) is a fundamental enzyme of nucleotide metabolism and one of the oldest anti-cancer targets. Beginning from the analysis of gene array data from the NCI-60 panel of cancer cell lines, we identified a significant correlation at both gene and protein level between TS and the markers of epithelial-to-mesenchymal transition (EMT), a developmental process that allows cancer cells to acquire features of aggressiveness, like motility and chemoresistance. TS levels were found to be significantly augmented in mesenchymal-like compared to epithelial-like cancer cells, to be regulated by EMT induction, and to negatively correlate with micro-RNAs (miRNAs) usually expressed in epithelial-like cells and known to actively suppress EMT...
March 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28323032/metabolic-re-wiring-of-isogenic-breast-epithelial-cell-lines-following-epithelial-to-mesenchymal-transition
#18
Skarphedinn Halldorsson, Neha Rohatgi, Manuela Magnusdottir, Kumari Sonal Choudhary, Thorarinn Gudjonsson, Erik Knutsen, Anna Barkovskaya, Bylgja Hilmarsdottir, Maria Perander, Gunhild M Mælandsmo, Steinn Gudmundsson, Óttar Rolfsson
Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#19
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
April 2017: Biochimie
https://www.readbyqxmd.com/read/28202352/amino-acid-transporter-slc38a3-promotes-metastasis-of-non-small-cell-lung-cancer-cells-by-activating-pdk1
#20
Yanhui Wang, Li Fu, Minqing Cui, Yongbin Wang, Yan Xu, Molin Li, Jun Mi
BACKGROUND: Tumor metastasis is a finely-tuned pathological process coupled to metabolic reprogramming that includes both glutamine and glucose. The solute carrier SLC38A3, a member of amino acid/polyamine/organocation (APC) superfamily, is an l-glutamine transporter. It is not clear whether SLC38A3 involves the metastasis of NSCLC (non small cell lung cancer). METHODS: The scratch test and transwell assay were used to determine the ability of NSCLC to migrate. Cellular amino acids content was determined by mass spectrometry...
February 13, 2017: Cancer Letters
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