Featured Research

from universities, journals, and other organizations

New factor to control oncogene-induced senescence discovered

Date:
May 21, 2013
Source:
Universidad de Barcelona
Summary:
A new article describes the major role that Pyruvate dehydrogenase (PDH) —- an enzyme of cellular energy metabolism -— plays in the regulation of the cellular senescence induced by the oncogene BRAF, which usually appears mutated in melanoma and other cancers.

An article published on the journal Nature describes the major role that Pyruvate dehydrogenase (PDH) -- an enzyme of cellular energy metabolism -- plays in the regulation of the cellular senescence induced by the oncogene BRAF, which usually appears mutated in melanoma and other cancers.

Related Articles


The researchers who participated in this international research are: Marta Cascante and Vitaly Selivanov, from the Department of Biochemistry and Molecular Biology of the Faculty of Biology of the UB and the Institute of Biomedicine of the University of Barcelona (IBUB), affiliated to the campus of International excellence Barcelona Knowledge Campus (BKC) ; Liang Zheng and Eyal Gottlieb, from Beatson Institute for Cancer Research (Scotland), and Joanna Kaplon and Daniel S. Peeper, from the Netherlands Cancer Institute, among other experts.

Cellular senescence: a 'brake' to cell division

Cellular senescence, formally described more than four decades ago by Paul Moorhead and Leonard Hayflick, is a tumour suppression mechanism which limits cell's ability to proliferate. This process works as a 'brake' for tumour genesis and can be an answer to several factors (oncogene, oxidative stress, telomere alterations, etc.)

Professor Marta Cascante, head of the Consolidated Research Group on Integrative Systems Biology, Metabolomics and Cancer of the UB honoured with the ICREA Academia Award 2010, explains that "as a response to an oncogene mutation, cell can activate its protection mechanisms and get into a phase so-called 'oncogene-induced senescence' which acts as a key tumour suppressive mechanism. In this phase, cell stops dividing and is in a premalignant state. However, when this 'brake' does not work correctly, the progression to a malignant state may happen and a tumour may appear. To identify which mechanisms regulate this cell phase is crucial to avoid tumour formation or reverse this process and to define future therapies."

PDH, a crucial mediator of oncogene-induced senescence

PDH is an enzyme complex located at the mitochondrial matrix regulated by phosphorylation (catalysed by PDH-inhibitory kinase) and dephosphorylation (catalysed by PDP2-activating phosphatase). Researchers prove that PDH is a crucial mediator of senescence induced by BRAF, an oncogene commonly mutated in melanoma and other cancers.

Authors affirm that BRAF-induced senescence is simultaneously accompanied by PDK1 inhibition and PDP2 activation. By means of these mechanisms, which converge on PDH activation, mitochondrial metabolism in BRAF-induced senescence is increased. The study also proves that senescence abrogation coincided with reversion of these processes.

According to researchers, PDK1 inhibition seems to cause induction of cellular senescence and regression of established melanomas. The results obtained from the inoculation of melanoma cell lines into immunocompromised mice prove almost complete tumour outgrowth prevention. And most importantly, PDK1 depletion in established melanomas leads to tumour regression.

The scientific team concludes that the activation of mitochondrial metabolism may contribute to reactive oxygen species (ROS) production, which play a relevant signalling function in cell metabolism and are involved in cellular senescence, telomere shortening and genome damage. Doctor Vitaly Selivanov, expert on metabolomics modelling and co-author of the article, explains that they got these results thanks to "the development of mathematic models which enabled to carry out a quantitative research of metabolic fluxes. Without this powerful mathematical analysis, it would be difficult to deeply understand what happens in cell metabolic reprogramming which causes tumour growth."


Story Source:

The above story is based on materials provided by Universidad de Barcelona. Note: Materials may be edited for content and length.


Journal Reference:

  1. Joanna Kaplon, Liang Zheng, Katrin Meissl, Barbara Chaneton, Vitaly A. Selivanov, Gillian Mackay, Sjoerd H. van der Burg, Elizabeth M. E. Verdegaal, Marta Cascante, Tomer Shlomi, Eyal Gottlieb, Daniel S. Peeper. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature, 2013; DOI: 10.1038/nature12154

Cite This Page:

Universidad de Barcelona. "New factor to control oncogene-induced senescence discovered." ScienceDaily. ScienceDaily, 21 May 2013. <www.sciencedaily.com/releases/2013/05/130521105559.htm>.
Universidad de Barcelona. (2013, May 21). New factor to control oncogene-induced senescence discovered. ScienceDaily. Retrieved November 25, 2014 from www.sciencedaily.com/releases/2013/05/130521105559.htm
Universidad de Barcelona. "New factor to control oncogene-induced senescence discovered." ScienceDaily. www.sciencedaily.com/releases/2013/05/130521105559.htm (accessed November 25, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, November 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins