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https://www.readbyqxmd.com/read/30080879/ubtor-kiaa1024-regulates-neurite-outgrowth-and-neoplasia-through-mtor-signaling
#1
Hefei Zhang, Quan Zhang, Ge Gao, Xinjian Wang, Tiantian Wang, Zhitao Kong, Guoxiang Wang, Cuizhen Zhang, Yun Wang, Gang Peng
The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS(G12V) induced neoplasia in the zebrafish...
August 6, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/30041196/targeting-of-the-c-jun-bcl-xl-p21-axis-accelerates-the-switch-from-senescence-to-apoptosis-upon-roc1-knockdown-in-gastric-cancer-cells
#2
Ping Chen, Xiaoting Luo, Zhihui Che, Wenli Zhang, Fuchen Liu, Daisen Hou, Dongqin Yang, Jie Liu
BACKGROUND/AIMS: Regulator of cullins-1 (ROC1) is a pivotal component of cullin-RING E3 ubiquitin ligases, which help to regulate distinct cellular processes by governing the degradation of various substrates. Because the role of ROC1 in gastric cancer is largely uncharacterized, we investigated the relationship between ROC1 expression and the prognosis of gastric cancer patients and explored the biological function of ROC1 and its underlying mechanisms in gastric cancer. METHODS: Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the correlation between the carcinogenesis of gastric cancer and ROC1...
July 24, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30029671/functional-and-genomic-analyses-reveal-therapeutic-potential-of-targeting-%C3%AE-catenin-cbp-activity-in-head-and-neck-cancer
#3
Vinay K Kartha, Khalid A Alamoud, Khikmet Sadykov, Bach-Cuc Nguyen, Fabrice Laroche, Hui Feng, Jina Lee, Sara I Pai, Xaralabos Varelas, Ann Marie Egloff, Jennifer E Snyder-Cappione, Anna C Belkina, Manish V Bais, Stefano Monti, Maria A Kukuruzinska
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of this disease. To date, few targeted therapies are available for HNSCC, and only a small fraction of patients have benefited from these treatments...
July 20, 2018: Genome Medicine
https://www.readbyqxmd.com/read/30010672/preclinical-assessment-of-the-bioactivity-of-the-anticancer-coumarin-ot48-by-spheroids-colony-formation-assays-and-zebrafish-xenografts
#4
Jin-Young Lee, Aloran Mazumder, Marc Diederich
In vitro and in vivo pre-clinical screening of novel therapeutic agents are an essential tool in cancer drug discovery. Although human cancer cell lines respond to therapeutic compounds in 2D (dimensional) monolayer cell cultures, 3D culture systems were developed to understand the efficacy of drugs in more physiologically relevant models. In recent years, a paradigm shift was observed in pre-clinical research to validate the potency of new molecules in 3D culture systems, more precisely mimicking the tumor microenvironment...
June 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29993186/theabrownin-triggers-dna-damage-to-suppress-human-osteosarcoma-u2os-cells-by-activating-p53-signalling-pathway
#5
Wangdong Jin, Li Zhou, Bo Yan, Li Yan, Fucun Liu, Peijian Tong, Wenhua Yu, Xiaoqiao Dong, Li Xie, Jin Zhang, Yiqiao Xu, Chunqi Li, Qiang Yuan, Letian Shan, Thomas Efferth
Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti-cancer activity. To evaluate its anti-osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy...
July 11, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29992995/angiotropism-and-extravascular-migratory-metastasis-in-cutaneous-and-uveal-melanoma-progression-in-a-zebrafish-model
#6
Giulia Fornabaio, Raymond L Barnhill, Claire Lugassy, Laurent A Bentolila, Nathalie Cassoux, Sergio Roman-Roman, Samar Alsafadi, Filippo Del Bene
Cutaneous melanoma is a highly aggressive cancer with a propensity for distant metastasis to various organs. In contrast, melanoma arising in pigmented uveal layers of the eye metastasizes mostly in the liver. The mechanisms of these metastases, which are ultimately resistant to therapy, are still unclear. Metastasis via intravascular dissemination of tumour cells is widely accepted as a central paradigm. However, we have previously described an alternative mode of tumour dissemination, extravascular migratory metastasis, based on clinical and experimental data...
July 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29903879/adipocyte-derived-lipids-mediate-melanoma-progression-via-fatp-proteins
#7
Maomao Zhang, Julie S Di Martino, Robert L Bowman, Nathaniel R Campbell, Sanjeethan C Baksh, Theresa Simon-Vermot, Isabella S Kim, Pearce Haldeman, Chandrani Mondal, Vladimir Yong-Gonzales, Mohsen Abu-Akeel, Taha Merghoub, Drew R Jones, Xiphias Ge Zhu, Arshi Arora, Charlotte E Ariyan, Kivanç Birsoy, Jedd D Wolchok, Katherine S Panageas, Travis Hollmann, Jose Javier Bravo-Cordero, Richard M White
Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface...
June 14, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29899843/induction-of-apoptosis-and-suppression-of-tumor-growth-by-nur77-derived-bcl-2-converting-peptide-in-chemoresistant-lung-cancer-cells
#8
Martin C Pearce, John T Gamble, Prasad R Kopparapu, Edmond F O'Donnell, Monica J Mueller, Hyo Sang Jang, Julie A Greenwood, Arnold C Satterthwait, Robert L Tanguay, Xiao-Kun Zhang, Siva Kumar Kolluri
Resistance to chemotherapy is a major cause of treatment failure and poor overall survival in patients with lung cancer. Identification of molecular targets present in resistant cancer cells is essential for addressing therapeutic resistance and prolonging lung cancer patient survival. Members of the B-cell lymphoma 2 (Bcl-2) family of proteins are associated with chemotherapeutic resistance. In this study, we found that pro-survival protein Bcl-2 is upregulated in paclitaxel resistant cells, potentially contributing to chemotherapy resistance...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29735912/towards-resolving-the-pro-and-anti-tumor-effects-of-the-aryl-hydrocarbon-receptor
#9
Supraja Narasimhan, Elizabeth Stanford Zulick, Olga Novikov, Ashley J Parks, Jennifer J Schlezinger, Zhongyan Wang, Fabrice Laroche, Hui Feng, Francesca Mulas, Stefano Monti, David H Sherr
We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose tumor aggression. Resolving this apparent contradiction is critical to the design of AHR-targeted cancer therapeutics. Molecular (siRNA, shRNA, AHR repressor, CRISPR-Cas9) and pharmacological (AHR inhibitors) approaches were used to confirm the hypothesis that AHR inhibition reduces human cancer cell invasion (irregular colony growth in 3D Matrigel cultures and Boyden chambers), migration (scratch wound assay) and metastasis (human cancer cell xenografts in zebrafish)...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29732557/overexpression-of-ezh2-in-conjunctival-melanoma-offers-a-new-therapeutic-target
#10
Jinfeng Cao, Kelly Cs Pontes, Renier C Heijkants, Niels J Brouwer, Arwin Groenewoud, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd van Duinen, Amina Fas Teunisse, Robert M Verdijk, Ewa Snaar-Jagalska, Aart G Jochemsen, Martine J Jager
Malignant melanoma of the conjunctiva (CM) is an uncommon but potentially deadly disorder. Many malignancies show an increased activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2). We studied whether EZH2 is expressed in CM, and whether it may be a target for therapy in this malignancy. Immunohistochemical analysis showed that EZH2 protein expression was absent in normal conjunctival melanocytes and primary acquired melanosis, while EZH2 was highly expressed in 13 (50%) of 26 primary CM and seven (88%) of eight lymph node metastases...
August 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29721065/development-of-a-novel-albumin-based-and-maleimidopropionic-acid-conjugated-peptide-with-prolonged-half-life-and-increased-in-vivo-anti-tumor-efficacy
#11
Junnan Feng, Chuanke Zhao, Lixin Wang, Like Qu, Hua Zhu, Zhi Yang, Guo An, Huifang Tian, Chengchao Shou
Angiogenesis plays a critical role in tumor aggressiveness, and a lot of anti-angiogenic agents have been used in clinical therapy. The therapeutic efficacy of peptides are generally restricted by the short in vivo life-time, thus, we were interested in developing a novel albumin-based and maleimidopropionic acid-conjugated peptide to prolong the half-life and improve the anti-tumor effect. Methods: We developed a peptide F56 with a maleimidopropionic acid (MPA) at the C-terminal (denoted as F56-CM), which allows immediate and irreversible conjugation with serum albumin...
2018: Theranostics
https://www.readbyqxmd.com/read/29712618/lymphatic-endothelium-stimulates-melanoma-metastasis-and-invasion-via-mmp14-dependent-notch3-and-%C3%AE-1-integrin-activation
#12
Pirita Pekkonen, Sanni Alve, Giuseppe Balistreri, Silvia Gramolelli, Olga Tatti-Bugaeva, Ilkka Paatero, Otso Niiranen, Krista Tuohinto, Nina Perälä, Adewale Taiwo, Nadezhda Zinovkina, Pauliina Repo, Katherine Icay, Johanna Ivaska, Pipsa Saharinen, Sampsa Hautaniemi, Kaisa Lehti, Päivi M Ojala
Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases...
May 1, 2018: ELife
https://www.readbyqxmd.com/read/29619196/dual-targeting-of-the-cancer-antioxidant-network-with-1-4-naphthoquinone-fused-gold-i-n-heterocyclic-carbene-complexes
#13
R McCall, M Miles, P Lascuna, B Burney, Z Patel, K J Sidoran, V Sittaramane, J Kocerha, D A Grossie, J L Sessler, K Arumugam, J F Arambula
To achieve a systems-based approach to targeting the antioxidant pathway, 1,4-naphthoquinone annulated N-heterocyclic carbene (NHC) [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] [silver(i) dichloride] ( 1 ), [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] chloride ( 2 ), and 1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i) chloride ( 3 )) were designed, synthesized, and tested for biological activity in a series of human cancer cell lines. The solution phase of complexes 1-3 were assigned using several spectroscopy techniques, including NMR spectroscopic analysis...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29579397/dicer1-deficiency-in-the-ipf-fibroblastic-focus-promotes-fibrosis-by-suppressing-microrna-biogenesis
#14
Jeremy Herrera, Daniel J Beisang, Mark Peterson, Colleen Forster, Adam Gilbertsen, Alexey Benyumov, Karen Smith, Christopher E Korenczuk, Victor H Barocas, Kacey Guenther, Ryan Hite, Lin Zhang, Craig A Henke, Peter B Bitterman
RATIONALE: The lung ECM in IPF mediates progression of fibrosis by decreasing fibroblast expression of microRNA-29 (miR-29), a master negative regulator of ECM production. The molecular mechanism is undefined. IPF ECM is stiffer than normal. Stiffness drives fibroblast ECM production in a YAP-dependent manner; and YAP is a known regulator of miR-29. Therefore, we tested the hypothesis that negative regulation of miR-29 by IPF ECM was mediated by mechanotransduction of stiffness. OBJECTIVES: To determine how IPF ECM negatively regulates miR-29...
March 26, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29570947/halogenated-bis-methoxybenzylidene-4-piperidone-curcuminoids-with-improved-anticancer-activity
#15
Florian Schmitt, Dharmalingam Subramaniam, Shrikant Anant, Subhash Padhye, Gerrit Begemann, Rainer Schobert, Bernhard Biersack
A series of readily available curcuminoids with a halogenated bis(4-methoxy/4,5-dimethoxybenzylidene)-4-piperidone structure were prepared and analyzed for their cytotoxic impact on eight human cancer cell lines of five different entities. The known 3,4,5-trimethoxybenzylidene curcuminoid 2 a and the new bis-(3-bromophenyl) and bis-(3,5-dibromophenyl) derivatives 3 c and 3 d proved to be more strongly antiproliferative than the known curcuminoid EF24 against six of these cell lines. Compounds 2 a and 3 c caused a distinct increase of reactive oxygen species, which eventually elicited apoptosis in 518A2 melanoma cells...
June 6, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29545747/cardiac-glycoside-glucoevatromonoside-induces-cancer-type-specific-cell-death
#16
Naira F Z Schneider, Claudia Cerella, Jin-Young Lee, Aloran Mazumder, Kyung Rok Kim, Annelise de Carvalho, Jennifer Munkert, Rodrigo M Pádua, Wolfgang Kreis, Kyu-Won Kim, Christo Christov, Mario Dicato, Hyun-Jung Kim, Byung Woo Han, Fernão C Braga, Cláudia M O Simões, Marc Diederich
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+ /K+ -ATPase α subunit, assessed by computational docking...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29541384/sox5-predicts-poor-prognosis-in-lung-adenocarcinoma-and-promotes-tumor-metastasis-through-epithelial-mesenchymal-transition
#17
Xin Chen, Yufei Fu, Hongfei Xu, Peng Teng, Qiong Xie, Yiran Zhang, Caochong Yan, Yiqiao Xu, Chunqi Li, Jianying Zhou, Yiming Ni, Weidong Li
Lung cancer is the leading cause of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) promotes lung cancer progression and metastasis, especially in lung adenocarcinoma. Sex determining region Y-box protein 5 (SOX5) is known to stimulate the progression of various cancers. Here, we used immunohistochemical analysis to reveal that SOX5 levels were increased in 90 lung adenocarcinoma patients. The high SOX5 expression in lung adenocarcinoma and non-tumor counterparts correlated with the patients' poor prognosis...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29515255/a-kinome-wide-rnai-screen-identifies-alk-as-a-target-to-sensitize-neuroblastoma-cells-for-hdac8-inhibitor-treatment
#18
Jing Shen, Sara Najafi, Sina Stäble, Johannes Fabian, Emily Koeneke, Fiona R Kolbinger, Jagoda K Wrobel, Benjamin Meder, Martin Distel, Tino Heimburg, Wolfgang Sippl, Manfred Jung, Heike Peterziel, Dominique Kranz, Michael Boutros, Frank Westermann, Olaf Witt, Ina Oehme
The prognosis of advanced stage neuroblastoma patients remains poor and, despite intensive therapy, the 5-year survival rate remains less than 50%. We previously identified histone deacetylase (HDAC) 8 as an indicator of poor clinical outcome and a selective drug target for differentiation therapy in vitro and in vivo. Here, we performed kinome-wide RNAi screening to identify genes that are synthetically lethal with HDAC8 inhibitors. These experiments identified the neuroblastoma predisposition gene ALK as a candidate gene...
March 7, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29499154/vangl2-rhoa-signaling-pathway-regulates-stem-cell-self-renewal-programs-and-growth-in-rhabdomyosarcoma
#19
Madeline N Hayes, Karin McCarthy, Alexander Jin, Mariana L Oliveira, Sowmya Iyer, Sara P Garcia, Sivasish Sindiri, Berkley Gryder, Zainab Motala, G Petur Nielsen, Jean-Paul Borg, Matt van de Rijn, David Malkin, Javed Khan, Myron S Ignatius, David M Langenau
Tumor growth and relapse are driven by tumor propagating cells (TPCs). However, mechanisms regulating TPC fate choices, maintenance, and self-renewal are not fully understood. Here, we show that Van Gogh-like 2 (Vangl2), a core regulator of the non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway, affects TPC self-renewal in rhabdomyosarcoma (RMS)-a pediatric cancer of muscle. VANGL2 is expressed in a majority of human RMS and within early mononuclear progenitor cells. VANGL2 depletion inhibited cell proliferation, reduced TPC numbers, and induced differentiation of human RMS in vitro and in mouse xenografts...
March 1, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29433678/wogonin-exacerbates-the-cytotoxic-effect-of-oxaliplatin-by-inducing-nitrosative-stress-and-autophagy-in-human-gastric-cancer-cells
#20
Zhi-Pan Hong, Li-Guo Wang, Hui-Juan Wang, Wei-Feng Ye, Xue-Zhi Wang
BACKGROUND: Gastric cancer remains one of the leading cause of death in the world. Drug combinations are potential approaches to provide more efficient treatments that minimize side effects. PURPOSE: We investigated the pharmacological effects of the combination of wogonin with oxaliplatin on gastric cancer cells in vitro and in vivo. METHODS AND RESULTS: In the present study, we found that wogonin enhanced the cytotoxicity of oxaliplatin; the drug combination resulted in strong synergistic inhibition of the cell viability in BGC-823 cells and in a zebrafish xenograft model...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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