The Experts below are selected from a list of 1132890 Experts worldwide ranked by ideXlab platform
Jacinta Serpa - One of the best experts on this subject based on the ideXlab platform.
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arl13b regulates breast Cancer Cell migration and invasion by controlling integrin mediated signaling
Cancers, 2019Co-Authors: Cristina Casalou, Alexandra Faustino, Ines Ferreira, Daniela Vaqueirinho, Pedro Castanheira, Teresa Barona, Andreia Ferreira, Jose S Ramalho, Fernanda Da Silva, Jacinta SerpaAbstract:Breast Cancer is the first cause of Cancer-related mortality among women worldwide, according to the most recent estimates. This mortality is mainly caused by the tumors’ ability to form metastases. Cancer Cell migration and invasion are essential for metastasis and rely on the interplay between actin cytoskeleton remodeling and Cell adhesion. Therefore, understanding the mechanisms by which Cancer Cell invasion is controlled may provide new strategies to impair Cancer progression. We investigated the role of the ADP-ribosylation factor (Arf)-like (Arl) protein Arl13b in breast Cancer Cell migration and invasion in vitro, using breast Cancer Cell lines and in vivo, using mouse orthotopic models. We show that Arl13b silencing inhibits breast Cancer Cell migration and invasion in vitro, as well as Cancer progression in vivo. We also observed that Arl13b is upregulated in breast Cancer Cell lines and patient tissue samples. Moreover, we found that Arl13b localizes to focal adhesions (FAs) and interacts with β3-integrin. Upon Arl13b silencing, β3-integrin Cell surface levels and FA size are increased and integrin-mediated signaling is inhibited. Therefore, we uncover a role for Arl13b in breast Cancer Cell migration and invasion and provide a new mechanism for how ARL13B can function as an oncogene, through the modulation of integrin-mediated signaling.
Peter V Hauschka - One of the best experts on this subject based on the ideXlab platform.
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notch3 in human breast Cancer Cell lines regulates osteoblast Cancer Cell interactions and osteolytic bone metastasis
American Journal of Pathology, 2010Co-Authors: Zhiyuan Zhang, Hao Wang, Sadakatsu Ikeda, Frederic H Fahey, Diane R Bielenberg, Patrick Smits, Peter V HauschkaAbstract:Breast Cancer preferentially metastasizes to bone. We therefore addressed the role of Notch signaling in osteoblast-Cancer Cell interactions and in bone metastasis. Human bone marrow osteoblasts selectively enhanced the expression of Notch3 and its ligand Jagged1 in human breast Cancer Cell lines. Osteoblasts also stimulated Cancer Cell colony formation in soft agar, which was reduced by a chemical inhibitor of Notch signaling and anti-transforming growth factor β1 (TGFβ1) antibody. TGFβ1, a major prometastatic product of osteoblasts, also stimulated Cancer Cell Notch3 expression. Notch3 knockdown in the Cancer Cells by stable short hairpin RNA interference decreased the osteoblast- and TGFβ1-stimulated colony formation as well as TGFβ1-mediated Smad3/Smad2 phosphorylation; Jagged1 level was coordinately reduced. In addition, expression of snail, a regulator of epithelial-mesenchymal transition, and the mesenchymal markers fibronectin and vimentin was attenuated by reducing Notch3 levels. To study the role of Notch3 signaling in bone metastasis, Cancer Cells were inoculated into athymic mice, either into femoral bone marrow cavities or into the systemic circulation via the left ventricle. Compared with robust osteolysis in mice receiving control Cells, osteolytic lesions were significantly reduced following inoculation of Cells with constitutively reduced Notch3 expression. Taken together, our results suggest that enhanced Notch3 expression in breast Cancer Cells, triggered by osteoblasts and their secretion of TGFβ1 in the bone marrow niche, may stand as a novel mechanism for promoting bone metastasis.
Jianxin Qiu - One of the best experts on this subject based on the ideXlab platform.
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downregulation of gas5 promotes bladder Cancer Cell proliferation partly by regulating cdk6
PLOS ONE, 2013Co-Authors: Zhihong Liu, Wei Wang, Juntao Jiang, Erdun Bao, Yigang Zeng, Le Tao, Jianxin QiuAbstract:UNLABELLED Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as transcriptional regulation, Cell growth and tumorigenesis. However, little is known about whether lncRNA-GAS5 (growth arrest-specific 5) regulates bladder Cancer progression. In the present study, we found that the GAS5 expression is commonly downregulated in bladder Cancer Cell lines and human specimens. Knockdown of GAS5 promotes bladder Cancer Cell proliferation, whereas forced expression of GAS5 suppresses Cell proliferation. We further demonstrated that knockdown of GAS5 increases CDK6 mRNA and protein levels in bladder Cancer Cells. Expectedly, GAS5 inhibition induces a significant decrease in G0/G1 phase and an obvious increase in S phase. Gain-of-function and loss-of-function studies showed that GAS5 inhibits bladder Cancer Cell proliferation, at least in part, by regulating CDK6 expression. CONCLUSIONS Downregulated GAS5 promotes bladder Cancer Cell proliferation, partly by regulating CDK6, and thus may be helpful in the development of effective treatment strategies against bladder Cancer.
Cristina Casalou - One of the best experts on this subject based on the ideXlab platform.
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arl13b regulates breast Cancer Cell migration and invasion by controlling integrin mediated signaling
Cancers, 2019Co-Authors: Cristina Casalou, Alexandra Faustino, Ines Ferreira, Daniela Vaqueirinho, Pedro Castanheira, Teresa Barona, Andreia Ferreira, Jose S Ramalho, Fernanda Da Silva, Jacinta SerpaAbstract:Breast Cancer is the first cause of Cancer-related mortality among women worldwide, according to the most recent estimates. This mortality is mainly caused by the tumors’ ability to form metastases. Cancer Cell migration and invasion are essential for metastasis and rely on the interplay between actin cytoskeleton remodeling and Cell adhesion. Therefore, understanding the mechanisms by which Cancer Cell invasion is controlled may provide new strategies to impair Cancer progression. We investigated the role of the ADP-ribosylation factor (Arf)-like (Arl) protein Arl13b in breast Cancer Cell migration and invasion in vitro, using breast Cancer Cell lines and in vivo, using mouse orthotopic models. We show that Arl13b silencing inhibits breast Cancer Cell migration and invasion in vitro, as well as Cancer progression in vivo. We also observed that Arl13b is upregulated in breast Cancer Cell lines and patient tissue samples. Moreover, we found that Arl13b localizes to focal adhesions (FAs) and interacts with β3-integrin. Upon Arl13b silencing, β3-integrin Cell surface levels and FA size are increased and integrin-mediated signaling is inhibited. Therefore, we uncover a role for Arl13b in breast Cancer Cell migration and invasion and provide a new mechanism for how ARL13B can function as an oncogene, through the modulation of integrin-mediated signaling.
Gregory V. Kryukov - One of the best experts on this subject based on the ideXlab platform.
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the landscape of Cancer Cell line metabolism
Nature Medicine, 2019Co-Authors: Shaoyang Ning, Gregory V. Kryukov, Mahmoud Ghandi, Shuba Gopal, Amy A Deik, Amanda Souza, Kerry A Pierce, Paula Keskula, Desiree Hernandez, Julie AnnAbstract:Despite considerable efforts to identify Cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and associated dependencies remain uncommon. To further understand the metabolic diversity of Cancer, we profiled 225 metabolites in 928 Cell lines from more than 20 Cancer types in the Cancer Cell Line Encyclopedia (CCLE) using liquid chromatography-mass spectrometry (LC-MS). This resource enables unbiased association analysis linking the Cancer metabolome to genetic alterations, epigenetic features and gene dependencies. Additionally, by screening barcoded Cell lines, we demonstrated that aberrant ASNS hypermethylation sensitizes subsets of gastric and hepatic Cancers to asparaginase therapy. Finally, our analysis revealed distinct synthesis and secretion patterns of kynurenine, an immune-suppressive metabolite, in model Cancer Cell lines. Together, these findings and related methodology provide comprehensive resources that will help clarify the landscape of Cancer metabolism.
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next generation characterization of the Cancer Cell line encyclopedia
Nature, 2019Co-Authors: Mahmoud Ghandi, Gregory V. Kryukov, Jordi Barretina, Franklin W Huang, Judit Janevalbuena, Robert E Mcdonald, Ellen GelfandAbstract:Large panels of comprehensively characterized human Cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven Cancer dependencies. To improve our understanding of the molecular features that contribute to Cancer phenotypes, including drug responses, here we have expanded the characterizations of Cancer Cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 Cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for Cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of Cancer research using model Cancer Cell lines.
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the Cancer Cell line encyclopedia enables predictive modelling of antiCancer drug sensitivity
Nature, 2012Co-Authors: Jordi Barretina, Nicolas Stransky, Joseph Lehar, Giordano Caponigro, Kavitha Venkatesan, Adam A Margolin, Sungjoon Kim, C Wilson, Gregory V. KryukovAbstract:The Cancer Cell Line Encyclopedia presents the first results from a large-scale screen of some 947 Cancer Cell lines with 24 antiCancer drugs, with the aim of identifying specific genomic alterations and gene expression profiles associated with selective sensitivity or resistance to potential therapeutic agents.