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https://www.readbyqxmd.com/read/28713289/mitochondrial-vdac1-a-key-gatekeeper-as-potential-therapeutic-target
#1
REVIEW
Amadou K S Camara, YiFan Zhou, Po-Chao Wen, Emad Tajkhorshid, Wai-Meng Kwok
Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713156/discovery-of-a-novel-calcium-sensitive-fluorescent-probe-for-%C3%AE-ketoglutarate
#2
Lin-Lin Gan, Lin-Hai Chen, Fa-Jun Nan
α-Ketoglutarate (α-KG), a pivotal metabolite in energy metabolism, has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers. It is recently proposed that plasma α-KG is a surrogate biomarker of NAFLD. Here, we report the development of a novel "turn-on" chemosensor for α-KG that contains a coumarin moiety as a fluorophore. Using benzothiazole-coumarin (BTC) as inspiration, we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for α-KG measurement...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28706220/opportunities-for-therapeutic-antibodies-directed-at-g-protein-coupled-receptors
#3
REVIEW
Catherine J Hutchings, Markus Koglin, William C Olson, Fiona H Marshall
G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases...
July 14, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28698214/papers-of-note-in-nature547-7661
#4
Annalisa M VanHook
This week's articles highlight progress in predicting T cell receptor specificity; an evolutionarily ancient form of antiviral defense; a mechanism of chemotherapy-induced cell death; metabolic rewiring in cancer cells; and structural insights into activation of a GPCR and of a mechanosensitive ion channel.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28692057/the-interactome-of-metabolic-enzyme-carbonic-anhydrase-ix-reveals-novel-roles-in-tumor-cell-migration-and-invadopodia-mmp14-mediated-invasion
#5
M Swayampakula, P C McDonald, M Vallejo, E Coyaud, S C Chafe, A Westerback, G Venkateswaran, J Shankar, G Gao, E M N Laurent, Y Lou, K L Bennewith, C T Supuran, I R Nabi, B Raught, S Dedhar
Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression. High confidence proteins identified include metabolic transporters, β1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14)...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28692053/pre-45s-rrna-promotes-colon-cancer-and-is-associated-with-poor-survival-of-crc-patients
#6
H Tsoi, K C Lam, Y Dong, X Zhang, C K Lee, J Zhang, S C Ng, S S M Ng, S Zheng, Y Chen, J Fang, J Yu
One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28685681/exploiting-cancer-metal-metabolism-using-anti-cancer-metal-binding-agents
#7
Angelica Merlot, Danuta Kalinowski, Zaklina Kovacevic, Patric Jansson, Sumit Sahni, Michael Huang, Darius Lane, Hiu Lok, Des Richardson
Metals are vital cellular elements necessary for multiple indispensable biological processes of living organisms, including energy transduction and cell proliferation. Interestingly, alterations in metal levels and also changes in the expression of proteins involved in metal metabolism have been demonstrated in a variety of cancers. Considering this and the important role of metals for cell growth, the development of drugs that sequester metals have become an attractive target for the development of novel anti-cancer agents...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#8
Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28623324/rapid-discrimination-of-human-oesophageal-squamous-cell-carcinoma-by-mass-spectrometry-based-on-differences-in-amino-acid-metabolism
#9
Zhang Jianyong, Xu Jianjun, Ouyang Yongzhong, Liu Junwen, Lu Haiyan, Yu Dongliang, Peng Jinhua, Xiong Junwen, Chen Huanwen, Wei Yiping
Oesophageal cancer (OC) is associated with high morbidity and mortality, and surgery is the most effective approach to treat it. In order to reduce surgical risks and duration of surgery, we explored a new strategy to determine tumour margins in surgery. In this study, we included 128 cancerous and 128 noncancerous database entries obtained from 32 human patients. Using internal extractive electrospray ionization-MS, in positive ion detection mode, the relative abundances of m/z 104.13, m/z 116.10, m/z 132...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617956/apigenin-induces-ros-dependent-apoptosis-and-er-stress-in-human-endometriosis-cells
#10
Sunwoo Park, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Apigenin is a plant-derived flavonoid having antiproliferative, anti-inflammatory, and anti-angiogenic properties in chronic and metabolic diseases, and cancers. However, the functional role of apigenin remains to be identified in human endometriosis that is a benign inflammatory disease causing infertility, dysmenorrhea, dyspareunia, and chronic abdominal or pelvic pain. In the present study, we determined the effects of apigenin on two well-established human endometriosis cell lines (VK2/E6E7 and End1/E6E7)...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28576319/chloroformate-derivatization-for-tracing-the-fate-of-amino-acids-in-cells-and-tissues-by-multiple-stable-isotope-resolved-metabolomics-msirm
#11
Ye Yang, Teresa W-M Fan, Andrew N Lane, Richard M Higashi
Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment...
July 11, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28574823/integrated-transcriptomic-analysis-of-distance-related-field-cancerization-in-rectal-cancer-patients
#12
Honglin Guo, Weigen Zeng, Lin Feng, Xuexin Yu, Ping Li, Kaitai Zhang, Zhixiang Zhou, Shujun Cheng
Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521016/influence-of-gsh-s-transferase-on-the-mutagenicity-induced-by-dichloromethane-and-1-2-dichloropropane
#13
Nozomi Akiba, Kazuhiro Shiizaki, Yoshitaka Matsushima, Osamu Endo, Kazuho Inaba, Yukari Totsuka
It has been suggested that dichloromethane (DCM) and 1,2-dichloropropane (DCP) are responsible for occupational cholangiocarcinoma. Dihaloalkanes are metabolically activated by GSH S-transferase theta1 (GSTT1) to yield products such as episulfonium ions. However, whether the GSTT1-mediated step of these dihaloalkanes is related to occupational cholangiocarcinoma is not known. In the present study, we investigated the influence of GSTT1 activation on the mutagenicity of DCM and 1,2-DCP using GSTT1-expressing Salmonella typhimurium TA100 (TA100-GST)...
May 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28516062/endoplasmic-reticulum-mitochondrial-ca-2-fluxes-underlying-cancer-cell-survival
#14
REVIEW
Hristina Ivanova, Martijn Kerkhofs, Rita M La Rovere, Geert Bultynck
Calcium ions (Ca(2+)) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER-mitochondria Ca(2+) transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER-mitochondrial Ca(2+) fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28478804/connexin-43-enhances-oxaliplatin-cytotoxicity-in-colorectal-cancer-cell-lines
#15
S Q Wang, S W Zhang, C Z Zhang, Z Y Zhao, Y J Wang
Oxaliplatin, a platinum-based chemotherapeutic agent, is an important first-line drug in the treatment of colorectal cancers, but drug resistance causes treatment failure. It has been reported that gap junctional communication can enhance the cytotoxicity of platinum drugs.  The gap junction formed of connexin proteins provides a direct pathway for electrical and metabolic cell-cell interaction. The voltage-dependent gating of gap junction allows small hydrophilic molecules and ions to permeate to adjacent cells...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28461251/mitophagy-and-age-related-pathologies-development-of-new-therapeutics-by-targeting-mitochondrial-turnover
#16
REVIEW
Konstantinos Palikaras, Ioanna Daskalaki, Maria Markaki, Nektarios Tavernarakis
Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis, ion homeostasis, lipid metabolism and initiation of apoptotic cell death. Proper mitochondrial physiology is a prerequisite for health and survival. Generation of new and removal of damaged or unwanted mitochondria are tightly controlled processes that need to be accurately coordinated for the maintenance of mitochondrial and cellular homeostasis...
April 28, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28457591/from-mucolipidosis-type-iv-to-ebola-trpml-and-two-pore-channels-at-the-crossroads-of-endo-lysosomal-trafficking-and-disease
#17
REVIEW
Christian Grimm, Elisabeth Butz, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
What do lysosomal storage disorders such as mucolipidosis type IV have in common with Ebola, cancer cell migration, or LDL-cholesterol trafficking? LDL-cholesterol, certain bacterial toxins and viruses, growth factors, receptors, integrins, macromolecules destined for degradation or secretion are all sorted and transported via the endolysosomal system (ES). There are several pathways known in the ES, e.g. the degradation, the recycling, or the retrograde trafficking pathway. The ES comprises early and late endosomes, lysosomes and recycling endosomes as well as autophagosomes and lysosome related organelles...
April 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28440547/development-of-lc-qtof-ms-method-for-human-lung-tissue-fingerprinting-a-preliminary-application-to-non-small-cell-lung-cancer
#18
Michal Ciborowski, Joanna Kisluk, Karolina Pietrowska, Paulina Samczuk, Ewa Parfieniuk, Tomasz Kowalczyk, Miroslaw Kozlowski, Adam Kretowski, Jacek Niklinski
The major histologic subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents yielded differences in outcomes according to histologic subgroups providing a rationale for histology-based treatment in NSCLC. Currently NSCLC subtyping is performed based on histopathological examinations and immunohistochemistry. However available methods leave about 10% of NSCLC cases as not otherwise specified...
April 25, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28417928/potential-coagulation-factor-driven-pro-inflammatory-responses-in-ovarian-cancer-tissues-associated-with-insufficient-o%C3%A2-and-plasma-supply
#19
REVIEW
Shiro Koizume, Yohei Miyagi
Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII). The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic blood coagulation process. Interactions between cancer cells and immune cells via coagulation factors and adhesion molecules can promote progression of cancer, including epithelial ovarian cancer (EOC). This process is not necessarily advantageous, as tumor tissues generally undergo hypoxia due to aberrant vasculature, followed by reduced access to plasma components such as coagulation factors...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416487/metabolic-markers-and-statistical-prediction-of-serous-ovarian-cancer-aggressiveness-by-ambient-ionization-mass-spectrometry-imaging
#20
Marta Sans, Kshipra Gharpure, Robert Tibshirani, Jialing Zhang, Li Liang, Jinsong Liu, Jonathan H Young, Robert L Dood, Anil K Sood, Livia S Eberlin
Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management...
April 17, 2017: Cancer Research
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