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https://www.readbyqxmd.com/read/28324269/metformin-sensitizes-triple-negative-breast-cancer-to-proapoptotic-trail-receptor-agonists-by-suppressing-xiap-expression
#1
Elena Strekalova, Dmitry Malin, Harisha Rajanala, Vincent L Cryns
PURPOSE: Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. METHODS: Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28302581/targeting-ets1-with-rnai-based-supramolecular-nanoassemblies-for-multidrug-resistant-breast-cancer-therapy
#2
Min Wu, Xingang Liu, Weihong Jin, Yongbing Li, Yang Li, Qinglian Hu, Paul K Chu, Guping Tang, Yuan Ping
Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically...
March 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28289921/genome-wide-in-vivo-rnai-screen-identifies-itih5-as-a-metastasis-suppressor-in-pancreatic-cancer
#3
Ken Sasaki, Hiroshi Kurahara, Eric D Young, Shoji Natsugoe, Asami Ijichi, Tomoo Iwakuma, Danny R Welch
The overwhelming majority of pancreatic ductal adenocarcinoma (PDAC) is not diagnosed until the cancer has metastasized, leading to an abysmal average life expectancy (3-6 months post-diagnosis). Earlier detection and more effective treatments have been hampered by inadequate understanding of the underlying molecular mechanisms controlling metastasis. We hypothesized that metastasis suppressors are involved in controlling metastasis in pancreatic cancer. Using an unbiased genome-wide shRNA screen, an shRNA library was transduced into the non-metastatic PDAC line S2-028 followed by intrasplenic injection...
March 13, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28285135/a-novel-transmembrane-protein-defines-the-endoplasmic-reticulum-stress-induced-cell-death-pathway
#4
Tomoya Tamaki, Kenta Kamatsuka, Taku Sato, Shuntaro Morooka, Kosuke Otsuka, Masahiro Hattori, Tomoyasu Sugiyama
Mitochondrial membrane potential (ΔΨm) maintenance is physiologically critical in cells; its loss causes apoptotic signalling and cell death. Accumulating DNA mutations and unfolded proteins in stressed cells activate signalling pathways for cell death induction. Cancer cells often fail to die even in the presence of some death signalling proteins. Here, we report a short hairpin RNA (shRNA) with an artificial sequence, denoted Psi1 shRNA, which leads to ΔΨm loss in HCT116 cells. The Psi1 shRNA target gene was shown to encode transmembrane protein 117 (TMEM117)...
March 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28277887/rnai-high-throughput-screening-of-single-and-multi-cell-type-tumor-spheroids-a-comprehensive-analysis-in-two-and-three-dimensions
#5
Jiaqi Fu, Daniel Fernandez, Marc Ferrer, Steven A Titus, Eugen Buehler, Madhu A Lal-Nag
The widespread use of two-dimensional (2D) monolayer cultures for high-throughput screening (HTS) to identify targets in drug discovery has led to attrition in the number of drug targets being validated. Solid tumors are complex, aberrantly growing microenvironments that harness structural components from stroma, nutrients fed through vasculature, and immunosuppressive factors. Increasing evidence of stromally-derived signaling broadens the complexity of our understanding of the tumor microenvironment while stressing the importance of developing better models that reflect these interactions...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28273451/interrogation-of-functional-cell-surface-markers-identifies-cd151-dependency-in-high-grade-serous-ovarian-cancer
#6
Mauricio Medrano, Laudine Communal, Kevin R Brown, Marcin Iwanicki, Josee Normand, Joshua Paterson, Fabrice Sircoulomb, Paul Krzyzanowski, Marian Novak, Sasha A Doodnauth, Fernando Suarez Saiz, Jane Cullis, Rima Al-Awar, Benjamin G Neel, John McPherson, Ronny Drapkin, Laurie Ailles, Anne-Marie Mes-Massons, Robert Rottapel
The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and comprehensive expression analysis of cell-surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28271570/single-domain-antibodies-for-the-knockdown-of-cytosolic-and-nuclear-proteins
#7
REVIEW
Thomas Böldicke
Single domain antibodies (sdAbs) from camels or sharks comprise only the variable heavy chain domain. Human sdAbs comprise the variable domain of the heavy chain (VH) or light chain (VL) and can be selected from human antibodies. SdAbs are stable, non aggregating molecules in vitro and in vivo compared to complete antibodies and scFv fragments. They are excellent novel inhibitors of cytosolic/nuclear proteins because they are correctly folded inside the cytosol in contrast to scFv fragments. SdAbs are unique because of their excellent specificity and possibility to target posttranslational modifications such as phosphorylation sites, conformers or interaction regions of proteins that cannot be targeted with genetic knockout techniques and are impossible to knockdown with RNAi...
March 8, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28263985/robust-stratification-of-breast-cancer-subtypes-using-differential-patterns-of-transcript-isoform-expression
#8
Thomas P Stricker, Christopher D Brown, Chaitanya Bandlamudi, Megan McNerney, Ralf Kittler, Vanessa Montoya, April Peterson, Robert Grossman, Kevin P White
Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes...
March 6, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28260073/foxm1-regulates-glycolysis-in-hepatocellular-carcinoma-by-transactivating-glucose-transporter-1-expression
#9
Runze Shang, Meng Pu, Yu Li, Desheng Wang
The Forkhead box M1 (FOXM1) transcription factor plays crucial roles in the initiation and progression of various malignancies, including hepatocellular carcinoma (HCC). However, the mechanism by which FOXM1 regulates cancer metabolism remains unclear. In the present study, overexpression and RNA interference (RNAi) approaches were used to investigate the role of FOXM1 in the regulation of glycolysis in vitro. Luciferase reporter assays were used to explore the transcriptional regulation of the glucose transporter 1 (GLUT1) promoter by FOXM1...
February 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259950/vinblastine-differs-from-taxol-as-it-inhibits-the-malignant-phenotypes-of-nsclc-cells-by-increasing-the-phosphorylation-of-op18-stathmin
#10
Fang Shen, Dan Long, Ting Yu, Xian Chen, Ying Liao, Yi Wu, Xuechi Lin
Taxol (paclitaxel) and vinblastine (VBL) are both efficacious chemotherapeutic agents that target the microtubules of tumor cells, but each functions in a mutual antagonistic manner. Op18/stathmin is a small molecular phosphoprotein which promotes depolymerization of microtubules. Non-small cell lung cancer (NSCLC) NCI-H1299 cells were employed to compare the curative effects of VBL and Taxol and explore the correlation between drug sensitivity and Op18/stathmin signaling. The present study found that VBL obviously promoted cellular apoptosis and initiated activation of caspase 3 and 9, and inhibited cell proliferation and colony formation, as well as cell migration in the NCI-H1299 cells in contrast with Taxol...
February 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259904/silencing-snail-suppresses-tumor-cell-proliferation-and-invasion-by-reversing-epithelial-to-mesenchymal-transition-and-arresting-g2-m-phase-in-non-small-cell-lung-cancer
#11
Xueying Yang, Mengmeng Han, Haibo Han, Bingjing Wang, Sheng Li, Zhiqian Zhang, Wei Zhao
Epithelial-to-mesenchymal transition (EMT) is essential for tumor invasion and metastasis. Snail has been proven to be a key regulator of EMT. Several studies have shown compelling evidence that Snail is also an important regulator of tumor growth and aggression; however, the role of Snail in the cell cycle has not been clarified. We decreased Snail expression by siRNA transfection and lentiviral‑mediated RNAi, to explore the effect of silencing Snail on the tumorigenicity and migration of lung carcinoma (lung cancer) cells...
February 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28249601/a-novel-foxo1-mediated-dedifferentiation-blocking-role-for-dkk3-in-adrenocortical-carcinogenesis
#12
Joyce Y Cheng, Taylor C Brown, Timothy D Murtha, Adam Stenman, C Christofer Juhlin, Catharina Larsson, James M Healy, Manju L Prasad, Wolfram T Knoefel, Andreas Krieg, Ute I Scholl, Reju Korah, Tobias Carling
BACKGROUND: Dysregulated WNT signaling dominates adrenocortical malignancies. This study investigates whether silencing of the WNT negative regulator DKK3 (Dickkopf-related protein 3), an implicated adrenocortical differentiation marker and an established tumor suppressor in multiple cancers, allows dedifferentiation of the adrenal cortex. METHODS: We analyzed the expression and regulation of DKK3 in human adrenocortical carcinoma (ACC) by qRT-PCR, immunofluorescence, promoter methylation assay, and copy number analysis...
March 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28248931/systematic-high-content-genome-wide-rnai-screens-of-endothelial-cell-migration-and-morphology
#13
Steven P Williams, Cathryn M Gould, Cameron J Nowell, Tara Karnezis, Marc G Achen, Kaylene J Simpson, Steven A Stacker
Many cell types undergo migration during embryogenesis and disease. Endothelial cells line blood vessels and lymphatics, which migrate during development as part of angiogenesis, lymphangiogenesis and other types of vessel remodelling. These processes are also important in wound healing, cancer metastasis and cardiovascular conditions. However, the molecular control of endothelial cell migration is poorly understood. Here, we present a dataset containing siRNA screens that identify known and novel components of signalling pathways regulating migration of lymphatic endothelial cells...
March 1, 2017: Scientific Data
https://www.readbyqxmd.com/read/28248929/rnai-screens-for-rho-gtpase-regulators-of-cell-shape-and-yap-taz-localisation-in-triple-negative-breast-cancer
#14
Patricia Pascual-Vargas, Samuel Cooper, Julia Sero, Vicky Bousgouni, Mar Arias-Garcia, Chris Bakal
In order to metastasise, triple negative breast cancer (TNBC) must make dynamic changes in cell shape. The shape of all eukaryotic cells is regulated by Rho Guanine Nucleotide Exchange Factors (RhoGEFs), which activate Rho-family GTPases in response to mechanical and informational cues. In contrast, Rho GTPase-activating proteins (RhoGAPs) inhibit Rho GTPases. However, which RhoGEFs and RhoGAPS couple TNBC cell shape to changes in their environment is very poorly understood. Moreover, whether the activity of particular RhoGEFs and RhoGAPs become dysregulated as cells evolve the ability to metastasise is not clear...
March 1, 2017: Scientific Data
https://www.readbyqxmd.com/read/28245869/regulation-of-stem-like-cancer-cells-by-glutamine-through-%C3%AE-catenin-pathway-mediated-by-redox-signaling
#15
Jianwei Liao, Pan-Pan Liu, Guoxin Hou, Jiajia Shao, Jing Yang, Kaiyan Liu, Wenhua Lu, Shijun Wen, Yumin Hu, Peng Huang
BACKGROUND: Cancer stem cells (CSCs) are thought to play an important role in tumor recurrence and drug resistance, and present a major challenge in cancer therapy. The tumor microenvironment such as growth factors, nutrients and oxygen affect CSC generation and proliferation by providing the necessary energy sources and growth signals. The side population (SP) analysis has been used to detect the stem-like cancer cell populations based on their high expression of ABCG2 that exports Hoechst-33342 and certain cytotoxic drugs from the cells...
February 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28245581/systematic-identification-and-assessment-of-therapeutic-targets-for-breast-cancer-based-on-genome-wide-rna-interference-transcriptomes
#16
Yang Liu, Xiaoyao Yin, Jing Zhong, Naiyang Guan, Zhigang Luo, Lishan Min, Xing Yao, Xiaochen Bo, Licheng Dai, Hui Bai
With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration...
February 24, 2017: Genes
https://www.readbyqxmd.com/read/28240870/a-multifunctional-envelope-type-sirna-delivery-nanoparticle-platform-for-prostate-cancer-therapy
#17
Xiaoding Xu, Jun Wu, Yanlan Liu, Phei Er Saw, Wei Tao, Mikyung Yu, Harshal R Zope, Michelle Si, Amanda Victorious, Jonathan Rasmussen, Dana Ayyash, Omid C Farokhzad, Jinjun Shi
With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular non-liver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery...
February 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28240737/fatty-acid-synthase-regulates-estrogen-receptor-%C3%AE-signaling-in-breast-cancer-cells
#18
J A Menendez, R Lupu
Fatty acid synthase (FASN), the key enzyme for endogenous synthesis of fatty acids, is overexpressed and hyperactivated in a biologically aggressive subset of sex steroid-related tumors, including breast carcinomas. Using pharmacological and genetic approaches, we assessed the molecular relationship between FASN signaling and estrogen receptor alpha (ERα) signaling in breast cancer. The small compound C75, a synthetic slow-binding inhibitor of FASN activity, induced a dramatic augmentation of estradiol (E2)-stimulated, ERα-driven transcription...
February 27, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28239766/up-regulation-of-gbp2-is-associated-with-neuronal-apoptosis-in-rat-brain-cortex-following-traumatic-brain-injury
#19
Qi Miao, Meihong Ge, Lili Huang
Guanylate binding protein 2 (GBP2) is one member of GBP family. Recently, GBP2 has been proposed to be a novel target of anti-cancer drugs. However, the role of GBP2 in the traumatic brain injury (TBI) is very limited. In this study, we sought to define GBP2's role in brain injury. GBP2 protein levels were significantly increased in the brain 3 days after injury, suggesting a functional role for GBP2 in TBI. Neuronal cells overexpressing GBP2 exhibited up-regulation of co-location of GBP2 and NeuN following TBI, suggesting that GBP2 potentiates the neuron apoptosis...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28235766/sigma1-targeting-to-suppress-aberrant-androgen-receptor-signaling-in-prostate-cancer
#20
Jeffrey D Thomas, Charles G Longen, Halley M Oyer, Nan Chen, Christina M Maher, Joseph M Salvino, Blase Kania, Kelsey N Anderson, William F Ostrander, Karen E Knudsen, Felix J Kim
Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways...
February 24, 2017: Cancer Research
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