Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay:
- Authors: de la Mare, Jo-Anne , Sterrenberg, Jason N , Sukhthankar, Mugdha G , Chiwakata, Maynard T , Beukes, Denzil R , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165184 , vital:41216 , DOI: 10.1186/1475-2867-13-39
- Description: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents.
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- Date Issued: 2013
Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
- Authors: Bodill, Taryn , Conibear, Anne C , Mutorwa, Marius K , Goble, Jessica L , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448912 , vital:74770 , xlink:href=""
- Description: DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand–receptor interactions.
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- Date Issued: 2013
Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines:
- Authors: Willmer, Tarryn , Contu, Lara , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165196 , vital:41217 , DOI: 10.1016/j.canlet.2012.09.021
- Description: The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.
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- Date Issued: 2013
The African coelacanth genome provides insights into tetrapod evolution:
- Authors: Amemiya, Chris T , Alföldi, Jessica , Lee, Alison P , Fan, Shaohua , Philippe, Herve´ , MacCallum, Iain , Braasch, Ingo , Manousaki, Tereza , Schneider, Igor , Rohner, Nicolas , Organ, Chris , Chalopin, Domitille , Smith, Jeramiah J , Robinson, Mark , Dorrington, Rosemary A , Gerdol, Marco , Aken, Bronwen , Biscotti, Maria Assunta , Barucca, Marco , Baurain, Denis , Berlin, Aaron , Blatch, Gregory L , Buonocore, Francesco , Burmester, Thorsten , Campbell, Michael S , Canapa, Adriana , Cannon, John P , Christoffels, Alan , De Moro, Gianluca , Edkins, Adrienne L , Fan, Lin , Fausto, Anna Maria , Feiner, Nathalie , Forconi, Mariko , Gamieldien, Junaid , Gnerre, Sante , Gnirke, Andreas , Goldstone, Jared V , Haerty, Wilfried , Hahn, Mark E , Hesse, Uljana , Hoffmann, Steve , Johnson, Jeremy , Karchner, Sibel I , Kuraku, Shigehiro , Lara, Marcia , Levin, Joshua Z , Litman, Gary W , Mauceli, Evan , Miyake, Tsutomu , Mueller, M Gail , Nelson, David R , Nitsche, Anne , Olmo, Ettore , Ota, Tatsuya , Pallavicini, Alberto , Panji, Sumir , Picone, Barbara , Ponting, Chris P , Prohaska, Sonja J , Przybylski, Dariusz , Ratan Saha, Nil , Ravi, Vydianathan , Ribeiro, Filipe J , Sauka-Spengler, Tatjana , Scapigliati, Giuseppe , Searle, Stephen M J , Sharpe, Ted , Simakov, Oleg , Stadler, Peter F , Stegeman, John J , Sumiyama, Kenta , Tabbaa, Diana , Tafer, Hakim , Turner-Maier, Jason , van Heusden, Peter , White, Simon , Williams, Louise , Yandell, Mark , Brinkmann, Henner , Volff, Jean-Nicolas , Tabin, Clifford J , Shubin, Neil , Schartl, Manfred , Jaffe, David B , Postlethwait, John H , Venkatesh, Byrappa , Di Palma, Frederica , Lander, Eric S , Meyer, Axel , Lindblad-Toh, Kerstin
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165030 , vital:41202 , DOI: 10.1038/nature12027
- Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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- Date Issued: 2013