Featured Research

from universities, journals, and other organizations

The Notch Gene Accelerates Colon Carcinogenesis

Date:
March 24, 2009
Source:
CNRS (Délégation Paris Michel-Ange)
Summary:
Scientists recently discovered how the Notch gene is involved in the pathogenic process leading to colon cancer. The Notch and Wnt signaling pathways play an important role in normal gut development and homeostasis. In mice, abnormal activation of these two signaling pathways increases the number of benign tumors—adenomas in the intestine by a factor of over twenty compared with activation of the Wnt pathway alone.

Professor Daniel Louvard (1) (CNRS Research Director and Director of the Curie Institute Research Centre) and his group, working in close partnership with Spyros Artavanis-Tsakonas (2), recently discovered how the Notch gene is involved in the pathogenic process leading to colon cancer. The Notch and Wnt signalling pathways play an important role in normal gut development and homeostasis.

In mice, abnormal activation of these two signalling pathways increases the number of benign tumours-adenomas-in the intestine by a factor of over twenty compared with activation of the Wnt pathway alone. Moreover, these tumours grow extremely fast in the colon, mimicking the pathogenic process observed in humans. Cooperative action between these two pathways creates a favourable environment for malignant transformation.

These findings (published online in PNAS) show that Notch acts as an "accelerator" in the development of colon cancer in humans, constituting an essential component of the pathogenic process. The question now is to find a "brake" that can counter this.

The gut, which represents a surface area equivalent to that of a tennis court, is in constant turnover completely renewing itself every five days. This turnover depends on the presence of stem cells and progenitor cells found in the crypts between intestinal villi. The stem cells give rise to progenitor cells which can in turn differentiate, over successive division cycles, to give the various different cell types that populate and form the gut. The key factor is to maintain a balance between differentiation and proliferation in the intestinal epithelium.

The Notch and Wnt signalling pathways are important in maintaining this balance, thereby ensuring normal development and organisation in the gut. These two systems control the proliferation and differentiation of stem cells in the intestinal crypts. The Wnt signalling pathway is tightly controlled by the APC (adenomatosis polyposis coli) gene which is associated with early-stage colon carcinogenesis: mutations in one of the two copies of this tumour suppressor gene underlie familial adenomatous polyposis, a condition characterised by the growth of hundreds or even thousands of polyps in the large intestine from adolescence on. This disease accounts for 1% of cases of colon cancer. The vast majority of sporadic cases of colon cancer are also associated with mutations in the APC gene.

The central Notch pathway

The Notch gene product acts as an "On/Off" switch. When it is On, the Notch protein triggers a cascade of intracellular signals essential to the development of all tissues in all multicellular organisms.

Notch is usually qualified as an oncogene and could represent a promising therapeutic target.

Professor Daniel Louvard, working together with Spyros Artavanis-Tsakonas, recently showed that the Notch and Wnt pathways act in concert to control the proliferation of progenitor cells in the gut. In animal models in which Wnt is aberrantly activated, the activation of Notch dramatically accelerates the rate of tumour formation in the gut, especially in the colon. In most mouse models, tumours are rarely found in the colon, unlike in human patients; the development of multiple adenomas in the mouse colon therefore mimics the human pathogenic process.

Such synergy between the Notch and Wnt genes has been observed in different animal models, suggesting that the mechanism is highly conserved throughout evolution. Professor Louvard states that "the Notch gene seems to act as an accelerator of colon carcinogenesis: its activation leads to increased cell division and therefore, an increased likelihood of mutation". However, malignant transformation requires a whole series of genetic events. Aberrant activation of the Notch and Wnt pathways creates a favourable environment for the accumulation of mutations that ultimately lead to colon cancer. Synergy of Notch and Wnt signals contributes to the earliest stages of tumourigenesis-when the tumours are referred to as polyps-the stage at which screening is so important.

Understanding the mechanisms involved in the formation, growth and transformation of these tumours will help in the search for novel therapeutic targets.

In 2005 in France, colon cancer struck more than 37,000 victims and caused 17,000 deaths. The chances of surviving this form of cancer (the third most common malignancy in the country) are closely linked to the stage at which the disease is diagnosed.

A mass colon cancer screening programme was set up at the end of 2008: every two years, everyone betwee n 50 and 74 will be sent a letter inviting them to ask their general practitioner about screening for colon cancer and consider, on a case by case basis, having a test to detect blood in their faeces.

(1) The Morphogenesis & Cell Signalling Group of the Curie Institute Cellular Compartmentalisation & Dynamics Unit; CNRS UMR144

(2) Professeur at the Collège de France and at Harvard Medical School (United States), and Director of the Curie Institute Genetics & Biology of Development Group; CNRS UMR3215/ Inserm U934

 


Story Source:

The above story is based on materials provided by CNRS (Délégation Paris Michel-Ange). Note: Materials may be edited for content and length.


Cite This Page:

CNRS (Délégation Paris Michel-Ange). "The Notch Gene Accelerates Colon Carcinogenesis." ScienceDaily. ScienceDaily, 24 March 2009. <www.sciencedaily.com/releases/2009/03/090318090437.htm>.
CNRS (Délégation Paris Michel-Ange). (2009, March 24). The Notch Gene Accelerates Colon Carcinogenesis. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2009/03/090318090437.htm
CNRS (Délégation Paris Michel-Ange). "The Notch Gene Accelerates Colon Carcinogenesis." ScienceDaily. www.sciencedaily.com/releases/2009/03/090318090437.htm (accessed April 24, 2014).

Share This



More Health & Medicine News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Fungus Killing Bats, Spreading in US

Deadly Fungus Killing Bats, Spreading in US

AP (Apr. 24, 2014) — A disease that has killed more than six million cave-dwelling bats in the United States is on the move and wildlife biologists are worried. White Nose Syndrome, discovered in New York in 2006, has now spread to 25 states. (April 24) Video provided by AP
Powered by NewsLook.com
Companies Ramp Up Wellness to Lower Health Costs

Companies Ramp Up Wellness to Lower Health Costs

AP (Apr. 24, 2014) — That little voice telling you to exercise, get in shape and get healthy is probably coming from your boss. More companies are beefing up wellness programs to try and cut down their health care costs. (April 24) Video provided by AP
Powered by NewsLook.com
Blood From World's Oldest Woman Suggests Life Limit

Blood From World's Oldest Woman Suggests Life Limit

Newsy (Apr. 24, 2014) — Scientists say for the extremely elderly, their stem cells might reach a state of exhaustion. This could limit one's life span. Video provided by Newsy
Powered by NewsLook.com
FDA Wants To Ban Sales Of E-Cigarettes To Minors

FDA Wants To Ban Sales Of E-Cigarettes To Minors

Newsy (Apr. 24, 2014) — The Food and Drug Administration wants to crack down on the use of e-cigarettes, banning the sale of the product to minors. 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:
from the past week

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