Posts By Giorgio
Proteolytic processing converts the repelling signal Sema3E into an inducer of invasive growth and lung metastasis
Cancer Res. 2005 Jul 15;65(14):6167-77.
Proteolytic processing converts the repelling signal Sema3E into an inducer of invasive growth and lung metastasis
Christensen C, Ambartsumian N, Gilestro GF, Thomsen B, Comoglio P, Tamagnone L, Guldberg P, Lukanidin E.We have previously shown that the expression of a semaphorin, known as a repelling cue in axon guidance, Sema3E, correlates with the ability to form lung metastasis in murine adenocarcinoma cell models. Now, besides providing evidence for the relevance of SEMA3E to human disease by showing that SEMA3E is frequently expressed in human cancer cell lines and solid tumors from breast cancer patients, we show biological activities of Sema3E, which support the implication of Sema3E in tumor progression and metastasis. In vivo, expression of Sema3E in mammary adenocarcinoma cells induces the ability to form experimental lung metastasis, and in vitro, the Sema3E protein exhibits both migration and growth promoting activity on endothelial cells and pheochromocytoma cells. This represents the first evidence of a metastasis-promoting function of a class 3 semaphorin, as this class of genes has hitherto been implicated in tumor biology only as tumor suppressors and negative regulators of growth. Moreover, we show that the full-size Sema3E protein is converted into a p61-Sema3E isoform due to furin-dependent processing, and by analyzing processing-deficient and truncated forms, we show that the generation of p61-Sema3E is required and sufficient for the function of Sema3E in lung metastasis, cell migration, invasive growth, and extracellular signal-regulated kinase 1/2 activation of endothelial cells. These findings suggest that certain breast cancer cells may increase their lung-colonizing ability by converting the growth repellent, Sema3E, into a growth attractant and point to a type of semaphorin signaling different from the conventional signaling induced by full-size dimeric class 3 semaphorins.
Plexin-B3 is a functional receptor for semaphorin 5A
EMBO Rep. 2004 Jul;5(7):710-4. Epub 2004 Jun 25.
Plexin-B3 is a functional receptor for semaphorin 5A
Artigiani S, Conrotto P, Fazzari P, Gilestro GF, Barberis D, Giordano S, Comoglio PM, Tamagnone L.Semaphorins are a large family of molecular cues implicated in neural development and in a variety of functions outside the nervous system. Semaphorin 5A (Sema5A) is a transmembrane semaphorin, containing seven thrombospondin type-1 repeats, which was recently found to control axon guidance. Here we show that plexin-B3 is a high-affinity receptor specific for Sema5A. We further demonstrate that plexin-B3 activation by Sema5A mediates functional responses in plexin-B3-expressing cells (either fibroblasts, epithelial and primary endothelial cells). In addition, Sema5A can trigger the intracellular signalling of the hepatocyte growth factor/scatter factor receptor, Met, associated in a complex with plexin-B3. We thus conclude that Sema5A is able to elicit multiple functional responses through its receptor plexin-B3.
The semaphorin 4D receptor controls invasive growth by coupling with Met
Nat Cell Biol. 2002 Sep;4(9):720-4.
The semaphorin 4D receptor controls invasive growth by coupling with Met
Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro GF, Barberis D, Tamagnone L, Comoglio PM.Semaphorins are cell surface and soluble signals that control axonal guidance. Recently, semaphorin receptors (plexins) have been discovered and shown to be widely expressed. Their biological activities outside the nervous system and the signal transduction mechanism(s) they utilize are largely unknown. Here, we show that in epithelial cells, Semaphorin 4D (Sema 4D) triggers invasive growth, a complex programme that includes cell#150;cell dissociation, anchorage-independent growth and branching morphogenesis. Interestingly, the same response is also controlled by scatter factors through their tyrosine kinase receptors, which share striking structural homology with plexins in their extracellular domain. We found that in cells expressing the endogenous proteins, Plexin B1 (the Sema 4D Receptor) and Met (the Scatter Factor 1/ Hepatocyte Growth Factor Receptor) associate in a complex. In addition, binding of Sema 4D to Plexin B1 stimulates the tyrosine kinase activity of Met, resulting in tyrosine phosphorylation of both receptors. Finally, cells lacking Met expression do not respond to Sema 4D unless exogenous Met is expressed. This work identifies a novel biological function of semaphorins and suggests the involvement of an unexpected signalling mechanism, namely, the coupling of a plexin to a tyrosine kinase receptor.
The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met
Nature. 2002 Mar 14;416(6877):187-90.
Petrelli A, Gilestro GF, Lanzardo S, Comoglio PM, Migone N, Giordano S.
CNR-CIOS and Department of Genetics, Biology and Biochemistry, University of Torino, 10126 Torino, Italy.
Ligand-dependent downregulation of tyrosine kinase receptors is a critical step for modulating their activity. Upon ligand binding, hepatocyte growth factor (HGF) receptor (Met) is polyubiquitinated and degraded; however, the mechanisms underlying HGF receptor endocytosis are not yet known. Here we demonstrate that a complex involving endophilins, CIN85 and Cbl controls this process. Endophilins are regulatory components of clathrin-coated vesicle formation. Through their acyl-transferase activity they are thought to modify the membrane phospholipids and induce negative curvature and invagination of the plasma membrane during the early steps of endocytosis. Furthermore, by means of their Src-homology 3 domains, endophilins are able to bind CIN85, a recently identified protein that interacts with the Cbl proto-oncogene. Cbl, in turn, binds and ubiquitinates activated HGF receptor, and by recruiting the endophilin-CIN85 complex, it regulates receptor internalization. Inhibition of complex formation is sufficient to block HGF receptor internalization and to enhance HGF-induced signal transduction and biological responses. These data provide further evidence of a relationship between receptor-mediated signalling and endocytosis, and disclose a novel functional role for Cbl in HGF receptor signalling.
Free unmissable Windows software that will make your computer life easier.
Whatever your job, there is a good chance you’ll spend lots of time sitting in front of a computer. If you do lots of data analysis, as I do lately, then you’ll find yourself in front of the monitor for most of the day. I’ll use this and the following few posts to introduce some softwares that are going to dramatically improve your productivity – and make your digital life easier. Web is full of list with dozens of best freeware software so I have no intention of making just another one; rather I will suggest one software per category. If you know of something better feel free to leave a comment to this post. I’ll start with this post with some more general softwares, useful to anyone. In the next one I will talk of more scientific-oriented softwares.
Fancy Pull-quotes (v0.85)
Installation.
Simply download the plugin, unzip it and copy the php file in the plugin directory of your wordpress installation. Then activate it from the admin panel and you are ready to go. The plugin is fully customizable from a page in the admin control panel.Note: if you are upgrading the plugin from an older version I recommend to first click the “restore all options to default” link.
How to use.
Simply surround the text that you want to see as pull-quote by the following tags: <!--pull--> and <!--/pull-->. The plugin will automatically scan your post for the text included with these tags and treat it as pull-quotes. Getting those nice effects is as easy as that! If you don’t like the tags as they are or if you want to change the look of the pulled quote, you can do it from the control page in the admin panel of wordpress. The quote is formatted using a CSS definition: if you are an advanced user (i.e. if you know a bit of CSS) you can hack the CSS style in every part.
Detailed instruction.
Open and Close tags: you can define which tag to be used as markers for the pulled quote. Default are <!–pull–> and <!–/pull–>. These tags are transparent by default meaning that if you check the “Mirror quote” option you can activate or inactivate the plugin at any time without changing the layout of your posts.
Background Color: Choose background color. Use same color as your normal background to make it transparent.
Text Color: Choose text color. You can use hexadecimal values (for instance: #0AFF44)
Max Width: specifies the maximal width allowed
Pullquote position: pullquote position in the page (left or right)
Border color, size, style: define border properties
Mirror quote: leave unchecked if you want to use a quote that won’t show in the text of your post (for instance: if you want to have the pullquote to appear at the very top of your post you can uncheck the “mirror quote” checkbox and insert the pulled quoted as first thing in your wordpress post)
Version.
Current version of the plugin is 0.85, released on 4.19.2007. The plugin has been tested and working WP 2.0.x and 2.1.x. If you have other experience on other versions of WP please leave a comment here and I’ll udate this paragraph.
License.
The plug-in is released under GPL license, meaning it’s free. If you like it or if you need help feel free to leave a comment here. (did you note that I installed some ads on this page? maybe you can find a couple of minute to check if there is anything interesting to you…)
Take a look also to my other plugin, Alt-to-Legend.
Enjoy!
Wikipedia, Citizendium, Frankenstein and the golem.
![[image by fd]](http://static.flickr.com/8/15327066_4f66fd82f2_m.jpg "[image by fd]")
Everybody knows Wikipedia so no need for introduction. Let’s just say that of the many very different opinions I have heard about it – placeable everywhere in the range from most celebratory to destructive – there is a quote that I find very attractive:
Wikipedia should not work, but it does!
This quote, which I believe is attributable to one of the fathers of wikpedia, Larry Sanger, says much about the on-line encyclopedia:
- Wikipedia is an experiment. A crazy one. Most people would have thought that the wiki affair would have been a failure but in fact it is now after only few years the biggest encyclopedia available nowadays.
Alt to Legend (v0.50)
Installation.
Simply download the plugin, unzip it and copy the php file in the plugin directory of your wordpress installation. Then activate it from the admin panel. You can customize the behavior of Alt-2-Legend from a new panel that will appear under the ‘Option’ page in the admin panel.
How to use.
Once your plugin is installed, it is ready to use. Simply insert an image in your post as you normally do and provide a description in the title textbox of the popup window. The text specified in the alt field or title field (your choice) will appear under the image. You can then decide the relative position of the images in the posts under the option page in the admin panel. Image can float always left, always right or according to the align parameter (meaning different post by post if you wish so).
Version.
Current version of the plugin is 0.5, released on 5.10.2009. The plugin has been tested only on WP 2.7.1. If you have other experience on other versions of WP please leave a comment here.
License.
The plug-in is released under GPL license, meaning it’s free. If you like it or if you need help feel free to leave a comment here – and hopefully I will get some monetary feedback from the people who will find interesting ads to click on.
History.
V0.1
-First release
V0.2
-Add a preview pane in the admin panel
-Add a easy-update link in the admin panel
-Set the width of the box sourrounding the image as big as the image itself
V0.3
-Fixed the ‘use no border’ bug
-Use local/relative URI for images hosted on localserver (solves error:
getimagesize(): URL file-access is disabled in the server configuration )
-Image can float constantly left, constantly right or left/right according to the align parameter
V0.35
-Fixed several bugs
-Add the padding and margin settings to adjust border of the image
V0.4
-Works with an unlimited number of images -Image box will fit also when image is resized using the width parameter
V0.5
-Will work only if image tag contains the magic word “alt2legend”.
E.g.:<img src="image.jpg" alt="This is a caption" alt2legend />
Also, included in wordpress plugin repository.
Take a look also to my other plugin, fancy-pullquotes.
Gattaca’s time.
X PRIZE Foundation is a non-profit foundation based in Santa Monica, CA. They gained popularity few years ago when they listed and subsequently awarded the Ansari X Prize. They offered US$10mln to the first private institution that would be able to launch a reusable manned spacecraft into space twice within two weeks. The price was awarded in 2004 and had a lot of echo. After that success, the X-Prize fondation grew stronger so that now they can efford to offer a new batch of prizes, related to different disciplines. One of them is the Archon X Prize for Genomics that also happened to be the largest medical prize in history. The prize is described as
A multi-million dollar incentive to create technology that can successfully map 100 human genomes in 10 days. The prize is designed to usher in a new era of personalized preventative medicine and stimulate new avenues of research and development of medical sciences.
What does it take to make a good Scientist?
I just saw something on the weekly edition of Nature Jobs that made me very happy. It is something that I was waiting to see since a long time. In May 2006 Georgia Chenevix-Trench felt like sharing some of her wisdom with the youngest public of the journal Nature. In the (often embarrassing) portion of the journal called Nature Jobs, she published a Decalogue with “tips for students”; goal of the letter was to provide prospective PhD students with rules of thumbs that would help out having a successful career. Sadly enough most of them were embracing the concept of hard work and only marginally important skills such as creativity, imagination, collaborative science.