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Your search keyword '"Scrace, Simon"' showing total 14 results
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14 results on '"Scrace, Simon"'

2. JUMP Cell Painting dataset: morphological impact of 136,000 chemical and genetic perturbations

Author

Chandrasekaran, Srinivas Niranj, primary, Ackerman, Jeanelle, additional, Alix, Eric, additional, Ando, D. Michael, additional, Arevalo, John, additional, Bennion, Melissa, additional, Boisseau, Nicolas, additional, Borowa, Adriana, additional, Boyd, Justin D., additional, Brino, Laurent, additional, Byrne, Patrick J., additional, Ceulemans, Hugo, additional, Ch’ng, Carolyn, additional, Cimini, Beth A., additional, Clevert, Djork-Arne, additional, Deflaux, Nicole, additional, Doench, John G, additional, Dorval, Thierry, additional, Doyonnas, Regis, additional, Dragone, Vincenza, additional, Engkvist, Ola, additional, Faloon, Patrick W., additional, Fritchman, Briana, additional, Fuchs, Florian, additional, Garg, Sakshi, additional, Gilbert, Tamara J., additional, Glazer, David, additional, Gnutt, David, additional, Goodale, Amy, additional, Grignard, Jeremy, additional, Guenther, Judith, additional, Han, Yu, additional, Hanifehlou, Zahra, additional, Hariharan, Santosh, additional, Hernandez, Desiree, additional, Horman, Shane R, additional, Hormel, Gisela, additional, Huntley, Michael, additional, Icke, Ilknur, additional, Iida, Makiyo, additional, Jacob, Christina B., additional, Jaensch, Steffen, additional, Khetan, Jawahar, additional, Kost-Alimova, Maria, additional, Krawiec, Tomasz, additional, Kuhn, Daniel, additional, Lardeau, Charles-Hugues, additional, Lembke, Amanda, additional, Lin, Francis, additional, Little, Kevin D., additional, Lofstrom, Kenneth R., additional, Lotfi, Sofia, additional, Logan, David J., additional, Luo, Yi, additional, Madoux, Franck, additional, Marin Zapata, Paula A., additional, Marion, Brittany A., additional, Martin, Glynn, additional, McCarthy, Nicola Jane, additional, Mervin, Lewis, additional, Miller, Lisa, additional, Mohamed, Haseeb, additional, Monteverde, Tiziana, additional, Mouchet, Elizabeth, additional, Nicke, Barbara, additional, Ogier, Arnaud, additional, Ong, Anne-Laure, additional, Osterland, Marc, additional, Otrocka, Magdalena, additional, Peeters, Pieter J., additional, Pilling, James, additional, Prechtl, Stefan, additional, Qian, Chen, additional, Rataj, Krzysztof, additional, Root, David E, additional, Sakata, Sylvie K., additional, Scrace, Simon, additional, Shimizu, Hajime, additional, Simon, David, additional, Sommer, Peter, additional, Spruiell, Craig, additional, Sumia, Iffat, additional, Swalley, Susanne E, additional, Terauchi, Hiroki, additional, Thibaudeau, Amandine, additional, Unruh, Amy, additional, Van de Waeter, Jelle, additional, Van Dyck, Michiel, additional, van Staden, Carlo, additional, Warchoł, Michał, additional, Weisbart, Erin, additional, Weiss, Amélie, additional, Wiest-Daessle, Nicolas, additional, Williams, Guy, additional, Yu, Shan, additional, Zapiec, Bolek, additional, Żyła, Marek, additional, Singh, Shantanu, additional, and Carpenter, Anne E., additional

Published
2023
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3. RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis:prev. Amoeboid cells are stem-like and induce non-cell autonomous metastasis in vivo

Author

Vlahov, Nikola, Steenbreek, Sander, Tognoli, Maria Laura, Pankova, Daniela, Eyres, Michael, Cano-Rodriguez, David, Scrace, Simon, von Kriegsheim, Alexander, Rots, Marianne, van Rheenen, Jacco, and O'Neill, Eric

Abstract

Activation of the GTPase RhoA increases actinomyosin contractility and a population of highly invasive amoeboid-like cells in tumours. Here we identified that the pro-metastatic oncogene RASSF1C is an activator of RhoA/ROCK signaling and amoeboid motility in cells with stem cell-like attributes. RhoA-driven amoeboid cell movement also induces the release of extracellular vesicles that promote non-cell autonomous migration and metastasis in recipient cells. Mechanistically, RASSF1C localises in the uropod like structure of fast A2-amoeboid motile cells where it activates pMLCII and supports contractility required for forward movement. In addition, amoeboid cells secret integrin-rich extracellular vesicles that support uropod attachment which are released in to the milieu upon initiation of movement. The higher level of amoeboid cells in RASSF1C+/RhoA+ tumours results in elevated A2 motility, an associated increase in vesicle release and promotion of metastasis in benign tumour cells in vivo, unravelling a common mechanism behind diverse phenotypic attributes of cancer cells.

Published
2022

4. RASSF1C oncogene elicits amoeboid invasion, cancer stemness and invasive EVs via a novel SRC/Rho axis

Author

Tognoli, Maria Laura, primary, Vlahov, Nikola, additional, Steenbeek, Sander, additional, Grawenda, Anna M., additional, Eyres, Michael, additional, Cano-Rodriguez, David, additional, Scrace, Simon, additional, Kartsonaki, Christiana, additional, von Kriegsheim, Alex, additional, Willms, Eduard, additional, Wood, Matthew J., additional, Rots, Marianne G., additional, van Rheenen, Jacco, additional, O’Neill, Eric, additional, and Pankova, Daniela, additional

Published
2021
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5. Novel regulation of SRC family kinase signalling by RASSF1 isoforms

Author

Scrace, S, Scrace, Simon, and O'Neill, E

Subjects
Medical Sciences, DNA damage signalling, Radiation, Oncology, Biology (medical sciences)
Abstract

RASSF1A is a tumour suppressor, the silencing of which occurs through promoter methylation in a variety of human cancers. Loss of RASSF1A is associated with decreased sensitivity to DNA damaging agents and worse prognosis in breast, colon and lung cancers amongst others. RASSF1A functions in a number of cellular processes, promoting apoptosis in response to DNA damage or death receptor signalling, or cell cycle arrest at both G1/S and pro-metaphase checkpoints. As a scaffold protein, RASSF1A imparts these functions through direct interaction with target proteins. We have identified a novel interaction between RASSF1A and the SRC activator, OSSA. Further studies identify a role for RASSF1 in SRC signalling. We find that a second isoform of RASSF1, RASSF1C, the expression of which is maintained in cancers, is able to activate SRC. We also identify a novel tumour suppressor role for RASSF1A inhibiting SRC activation through binding of RASSF1C. SRC activation by RASSF1C expression promotes internalisation of adherens junctions leading to subsequent loss of tight junctions and cell polarity markers from sites of cell-cell contact. -catenin is also found to be re-localised throughout the cells from where it is hypothesised to be able to upregulate pro-proliferative genes. In addition, we find that RASSF1C expression promotes cell motility in both scratch wound and transwell assays. Finally, we show that RASSF1C expression enhances tumour cell aggressiveness using a mammosphere growth assay. We conclude that RASSF1C is an oncogene that can promote EMT through the activation of SRC family kinases. This function is inhibited by the tumour suppressor RASSF1A. This work highlights why RASSF1A is lost through epigenetic mechanisms and not mutation and why loss of RASSF1A is associated with more aggressive, metastatic cancers.

Published
2016

6. Abstract 5160: Development of REDX05358, a novel highly selective and potent pan RAF inhibitor and a potential therapeutic for BRAF and RAS mutant tumors

Author

Mason, Helen, primary, Scrace, Simon, additional, Testar, Richard, additional, Rainard, Julie, additional, Talab, Fatima, additional, Poonawala, Ryaka, additional, Smith, Philippa, additional, Brooke, Harriet, additional, Frith, Sarah, additional, Ahmet, Jonathan, additional, Hall, Jonathan, additional, Sorrell, David, additional, Moore, Jon, additional, Phillips, Caroline, additional, France, Dennis, additional, Bingham, Matilda, additional, and Armer, Richard, additional

Published
2017
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8. Abstract B66: An integrated immuno-oncology platform using high-throughput cell based assays, gene editing and genomic screens in immune cells

Author

Frank, An, primary, Kumar, Sujatha, additional, Ghirelli, Christina, additional, Hoenderdos, Kim, additional, Huseni, Tabasum, additional, Thibault, Lauren, additional, Kifle, Lydia, additional, Almog, Nava, additional, Zhao, Felicia, additional, Scrace, Simon, additional, Myaskovsky, Anatoly, additional, Lowe, Chris, additional, Steiger, Janine, additional, McCarthy, Nicola, additional, and Moore, Jonathan, additional

Published
2017
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11. Alternate RASSF1 Transcripts Control SRC Activity, E-Cadherin Contacts, and YAP-Mediated Invasion

Author

Vlahov, Nikola, primary, Scrace, Simon, additional, Soto, Manuel Sarmiento, additional, Grawenda, Anna M., additional, Bradley, Leanne, additional, Pankova, Daniela, additional, Papaspyropoulos, Angelos, additional, Yee, Karen S., additional, Buffa, Francesca, additional, Goding, Colin R., additional, Timpson, Paul, additional, Sibson, Nicola, additional, and O’Neill, Eric, additional

Published
2015
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12. Identification of novel,in vivoactive Chk1 inhibitors utilizing structure guided drug design

Author

Massey, Andrew J., primary, Stokes, Stephen, additional, Browne, Helen, additional, Foloppe, Nicolas, additional, Fiumana, Andreá, additional, Scrace, Simon, additional, Fallowfield, Mandy, additional, Bedford, Simon, additional, Webb, Paul, additional, Baker, Lisa, additional, Christie, Mark, additional, Drysdale, Martin J., additional, and Wood, Mike, additional

Published
2015
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14. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design.

Author

Massey AJ, Stokes S, Browne H, Foloppe N, Fiumana A, Scrace S, Fallowfield M, Bedford S, Webb P, Baker L, Christie M, Drysdale MJ, and Wood M

Subjects
Animals, Apoptosis drug effects, Camptothecin analogs & derivatives, Camptothecin pharmacology, Cell Cycle drug effects, Cell Line, Tumor, Checkpoint Kinase 1, Drug Design, Drug Synergism, Female, Humans, Irinotecan, Mice, Mice, Nude, Structure-Activity Relationship, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colonic Neoplasms drug therapy, Indoles pharmacology, Protein Kinase Inhibitors pharmacology, Protein Kinases metabolism, Pyridones pharmacology
Abstract

Chk1 kinase is a critical component of the DNA damage response checkpoint especially in cancer cells and targeting Chk1 is a potential therapeutic opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy drugs. Fragment elaboration by structure guided design was utilized to identify and develop a novel series of Chk1 inhibitors culminating in the identification of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine, cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411 showed minimal toxicity as a single agent and in combination with irinotecan. In tumor bearing animals, V158411 was detected at high levels in the tumor with a long elimination half-life; no pharmacologically significant in vivo drug-drug interactions with irinotecan were identified through analysis of the pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of irinotecan in a variety of human colon tumor xenograft models without additional systemic toxicity. These results demonstrate the opportunity for combining V158411 with standard of care chemotherapeutic agents to potentiate the therapeutic efficacy of these agents without increasing their toxicity to normal cells. Thus, V158411 would warrant further clinical evaluation.

Published
2015
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