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https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#1
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641978/angptl4-t266m-variant-is-associated-with-reduced-cancer-invasiveness
#2
Zhen Wei Tan, Ziqiang Teo, Carol Tan, Chee Chong Choo, Wei Sheng Loo, Yiyang Song, Zhi Yang Tam, Sean Pin Ng, Hong Zheng Koh, Yi Siang Ng, Susana Geifman Shochat, Yin Hoe Yau, Pengcheng Zhu, Nguan Soon Tan
Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form a N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes. In this study, we compared the characteristics of tumors with and without wild-type (wt) cANGPTL4 and tumors with cANGPTL4 bearing the T266M mutation (T266M cANGPTL4)...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#3
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604746/oncogenic-k-ras-upregulates-itga6-expression-via-fosl1-to-induce-anoikis-resistance-and-synergizes-with-%C3%AE-v-class-integrins-to-promote-emt
#4
K Zhang, S-M Myllymäki, P Gao, R Devarajan, V Kytölä, M Nykter, G-H Wei, A Manninen
In many cancer types, integrin-mediated signaling regulates proliferation, survival and invasion of tumorigenic cells. However, it is still unclear how integrins crosstalk with oncogenes to regulate tumorigenesis and metastasis. Here we show that oncogenic K-Ras(V12) upregulates α6-integrin expression in Madin-Darby canine kidney (MDCK) cells via activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)/Fos-related antigen 1-signaling cascade. Activated α6-integrins promoted metastatic capacity and anoikis resistance, and led to perturbed growth of MDCK cysts...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28592291/tightly-controlled-mrtf-a-activity-regulates-epithelial-differentiation-during-formation-of-mammary-acini
#5
Anja Seifert, Guido Posern
BACKGROUND: Myocardin-related transcription factors (MRTF) A and B link actin dynamics and mechanotransduction to gene expression. In mice, MRTF-A is involved in mammary gland differentiation, but its role in human mammary epithelial cells remains unclear. METHODS: Three-dimensional cultures of human mammary epithelial MCF10A cells were used to model acinar morphogenesis. Stable MRTF-A knockdown, MRTF-A/B rescue and MRTF-A/B overexpression was established to characterize the functional role during morphogenesis using confocal microscopy and expression analysis...
June 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28591719/stable-and-high-expression-of-galectin-8-tightly-controls-metastatic-progression-of-prostate-cancer
#6
Lucas Daniel Gentilini, Felipe Martín Jaworski, Carolina Tiraboschi, Ignacio González Pérez, Monica Lidia Kotler, Anne Chauchereau, Diego Jose Laderach, Daniel Compagno
Two decades ago, Galectin-8 was described as a prostate carcinoma biomarker since it is only expressed in the neoplastic prostate, but not in the healthy tissue. To date, no biological function has been attributed to Galectin-8 that could explain this differential expression. In this study we silenced Galectin-8 in two human prostate cancer cell lines, PC3 and IGR-CaP1, and designed a pre-clinical experimental model that allows monitoring the pathology from its early steps to the long-term metastatic stages...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589906/loss-of-calponin-h1-confers-anoikis-resistance-and-tumor-progression-in-the-development-of-high-grade-serous-carcinoma-originating-from-the-fallopian-tube-epithelium
#7
Kai-Hung Wang, Sung-Chao Chu, Tang-Yuan Chu
Increasing evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from the fallopian tube epithelium and metastasizes to the ovary as the secondary site. A working hypothesis is that detached tubal HGSC cells survive anoikis and implant on the ovary. In this study, we found that downregulation of calponin h1 (CNN1) is necessary for the anoikis survival and cell transformation. CNN1 was progressively downregulated in cells and tissues representing different stages of HGSC development from fallopian tube epithelium (FTE)...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28574839/advances-in-single-cell-rna-sequencing-and-its-applications-in-cancer-research
#8
REVIEW
Sibo Zhu, Tao Qing, Yuanting Zheng, Li Jin, Leming Shi
Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years' development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570738/cellular-senescence-is-associated-with-human-retinal-microaneurysm-formation-during-aging
#9
Mariana López-Luppo, Joana Catita, David Ramos, Marc Navarro, Ana Carretero, Luísa Mendes-Jorge, Pura Muñoz-Cánoves, Alfonso Rodriguez-Baeza, Victor Nacher, Jesus Ruberte
Purpose: Microaneurysms are present in healthy old-age human retinas. However, to date, no age-related pathogenic mechanism has been implicated in their formation. Here, cellular senescence, a hallmark of aging and several age-related diseases, has been analyzed in the old-age human retina and in the retina of a progeric mouse. Methods: Retinas were obtained from 17 nondiabetic donors and from mice deficient in Bmi1. Cellular senescence was analyzed by immunohistochemistry, senescent-associated β-galactosidase activity assay, Sudan black B staining, conventional transmission electron microscopy, and immunoelectronmicroscopy...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28532603/matrix-replenishing-by-bmscs-is-beneficial-for-osteoarthritic-temporomandibular-joint-cartilage
#10
M Zhang, H Yang, L Lu, X Wan, J Zhang, H Zhang, X Liu, X Huang, G Xiao, M Wang
OBJECTIVES: The present goal was to explore whether matrix replenishment is the primary requirement for osteoarthritic (OA) cartilage. METHODS: Cells isolated from the superficial and deep zone cartilage of a pig temporomandibular joint (TMJ) were exposed to fluid flow shear stress (FFSS). Differences in matrix production and cellular differentiation were detected. Unilateral anterior crossbite (UAC) was applied to C57BL/6J female mice. Green fluorescent protein-labeled exogenous bone marrow stromal cells (GFP-BMSCs) were injected weekly into TMJs, starting from 3 weeks of UAC stimulation and continuing for 4-, 8- and 12-weeks...
May 19, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28510655/mir-145-promoted-anoikis-resistance-in-tumor-endothelial-cells
#11
Kyoko Hida, Taisuke Kawamoto, Nako Maishi, Masahiro Morimoto, Kosuke Akiyama, Noritaka Ohga, Masanobu Shindoh, Nobuo Shinohara, Yasuhiro Hida
Tumor progression is dependent on tumor angiogenesis. We previously reported that the phenotype of tumor endothelial cells (TECs) is distinct from normal endothelial cells (NECs). Herein, we conducted a pathway analysis using a public TEC microarray database and identified several putative TEC-specific miRNAs. We found that miR-145 expression was upregulated in TECs and that miR-145 enhanced cell adhesion and anoikis resistance and upregulated Bcl-2 and Bcl-xl via ERK1/2in human microvascular endothelial cells...
May 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28506645/multiple-roles-of-glyoxalase-1-mediated-suppression-of-methylglyoxal-glycation-in-cancer-biology-involvement-in-tumour-suppression-tumour-growth-multidrug-resistance-and-target-for-chemotherapy
#12
REVIEW
Naila Rabbani, Mingzhan Xue, Martin O Weickert, Paul J Thornalley
Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all human cells. It catalyses the glutathione-dependent removal of the endogenous reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side product of anaerobic glycolysis. It modifies protein and DNA to form mainly hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal accumulation of MG, dicarbonyl stress, increases adduct levels which may induce apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a tumour suppressor protein and small molecule inducers of Glo1 expression may find use in cancer prevention...
May 12, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28496098/combined-treatment-with-metformin-and-2-deoxy-glucose-induces-detachment-of-viable-mda-mb-231-breast-cancer-cells-in-vitro
#13
Maruša Bizjak, Petra Malavašič, Klemen Dolinar, Jelka Pohar, Sergej Pirkmajer, Mojca Pavlin
Triple naegative breast cancer has an increased rate of distant metastasis and consequently poor prognosis. To metastasize, breast cancer cells must detach from the main tumour mass and resist anoikis, a programmed cell death induced by lack of cell-extracellular matrix communication. Although cancer cells must detach to metastasize in vivo, the viability of floating cancer cells in vitro is rarely investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231 cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of floating cells, of which about 95% were viable...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28492548/inhibition-of-ptp1b-disrupts-cell-cell-adhesion-and-induces-anoikis-in-breast-epithelial-cells
#14
Bylgja Hilmarsdottir, Eirikur Briem, Skarphedinn Halldorsson, Jennifer Kricker, Sævar Ingthorsson, Sigrun Gustafsdottir, Gunhild M Mælandsmo, Magnus K Magnusson, Thorarinn Gudjonsson
Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28484606/an-agent-based-model-of-anoikis-in-the-colon-crypt-displays-novel-emergent-behaviour-consistent-with-biological-observations
#15
Tim Ingham-Dempster, Dawn C Walker, Bernard M Corfe
Colorectal cancer (CRC) is a major cause of cancer mortality. Colon crypts are multi-cellular flask-shaped invaginations of the colonic epithelium, with stem cells at their base which support the continual turnover of the epithelium with loss of cells by anoikis from the flat mucosa. Mutations in these stem cells can become embedded in the crypts, a process that is strongly implicated in CRC initiation. We describe a computational model which includes novel features, including an accurate representation of the geometry of the crypt mouth...
April 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28482619/14-3-3%C3%AF-downregulation-suppresses-icc-metastasis-via-impairing-migration-invasion-and-anoikis-resistance-of-icc-cells
#16
Zhenjie Yang, Qianjun Jin, Wendi Hu, Longfei Dai, Zhengze Xue, Da Man, Lin Zhou, Haiyang Xie, Jian Wu, Shusen Zheng
BACKGROUND: 14-3-3σ protein plays an important role in multiple cellular processes. The role of 14-3-3σ in the progression of intrahepatic cholangiocarcinoma (ICC) has not been well understood. OBJECTIVE: We performed this research to explore the relationship between 14-3-3σ level and clinical characteristics and prognosis of ICC patients. Besides, we used ICC cell lines HCCC-9810 and RBE to assess the biological function of 14-3-3σ. METHODS: We examined 14-3-3σ expression in 28 ICC tissues and matched paratumor tissues by quantitative real-time PCR and immunohistochemistry...
April 28, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28481878/the-ap-1-transcription-factor-fosl1-causes-melanocyte-reprogramming-and-transformation
#17
K Maurus, A Hufnagel, F Geiger, S Graf, C Berking, A Heinemann, A Paschen, S Kneitz, C Stigloher, E Geissinger, C Otto, A Bosserhoff, M Schartl, S Meierjohann
The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28471257/ras-ling-with-new-therapeutic-targets-for-metastasis
#18
Joshua A Mason, Zachary T Schafer
Successful cancer metastasis relies on the ability of cancer cells to survive independently of attachment to the extracellular matrix (ECM) and to overcome ECM-detachment-induced death programs. This can be accomplished through activating mutations in cellular oncogenes that subsequently lead to the inhibition of anoikis and to alterations in productive metabolism. One example of such an oncogene is Ras which is found to be mutated and hyperactivated in a variety of distinct cancers. Despite numerous studies on Ras, the precise molecular mechanisms that facilitate survival during ECM-detachment remain poorly understood...
May 4, 2017: Small GTPases
https://www.readbyqxmd.com/read/28468950/er-stress-dependent-microparticles-derived-from-smooth-muscle-cells-promote-endothelial-dysfunction-during-thoracic-aortic-aneurysm-and-dissection
#19
Li-Xin Jia, Wen-Mei Zhang, Tao-Tao Li, Yan Liu, Chun-Mei Piao, You-Cai Ma, Yu Lu, Yuan Wang, Ting-Ting Liu, Yong-Fen Qi, Jie Du
The degeneration of vascular smooth muscle cell(s) (SMC) is one of the key features of thoracic aortic aneurysm and dissection (TAAD). We and others have shown that elevated endoplasmic reticulum (ER) stress causes SMC loss and TAAD formation, however, the mechanism of how SMC dysfunction contributes to intimal damage, leading to TAAD, remains to be explored. In the present study, in vitro assay demonstrated that elevated mechanical stretch (18% elongation, 3600 cycles/h) stimulated the ER stress response and microparticle(s) (MP) production from both SMC and endothelial cell(s) (EC) in a time-dependent manner...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28448014/an-efficient-and-flexible-cell-aggregation-method-for-3d-spheroid-production
#20
Sarah M Maritan, Eric Y Lian, Lois M Mulligan
Monolayer cell culture does not adequately model the in vivo behavior of tissues, which involves complex cell-cell and cell-matrix interactions. Three-dimensional (3D) cell culture techniques are a recent innovation developed to address the shortcomings of adherent cell culture. While several techniques for generating tissue analogues in vitro have been developed, these methods are frequently complex, expensive to establish, require specialized equipment, and are generally limited by compatibility with only certain cell types...
March 27, 2017: Journal of Visualized Experiments: JoVE
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