Featured Research

from universities, journals, and other organizations

Key regulator of colon cancer discovered

Date:
March 27, 2014
Source:
Institute for Research in Biomedicine (IRB Barcelona)
Summary:
P38 is required for the survival and proliferation of colon cancer cells, thus favoring tumor growth, researchers have discovered. The study demonstrates that, on the one hand, p38 is important for the optimal maintenance of the epithelial barrier that protects the intestine against toxic agents, thus contributing to decreased tumor development. Intriguingly, on the other hand, once a tumor has formed, p38 is required for the survival and proliferation of colon cancer cells, thus favoring tumor growth.

A team headed by Angel R. Nebreda at the Institute for Research in Biomedicine (IRB) identifies a dual role of the p38 protein in colon cancer. The study demonstrates that, on the one hand, p38 is important for the optimal maintenance of the epithelial barrier that protects the intestine against toxic agents, thus contributing to decreased tumor development. Intriguingly, on the other hand, once a tumor has formed, p38 is required for the survival and proliferation of colon cancer cells, thus favoring tumor growth. The study is published today in Cancer Cell, a journal with one of the highest impact factors in cancer research.

p38 enhances the survival of colon cancer cells

The protein p38 is a member of the MAPK family -- molecules that transmit signals from outside the cell inside, thus allowing an appropriate and dynamic cell response. This protein is expressed in all cells of the body and it performs highly diverse functions depending on the context and tissue involved. Nebreda's group at IRB focuses on the function of p38 in cancer. Their work describes the essential role of p38 in tumor progression for the first time in vivo. Furthermore, the scientists demonstrate that the treatment of mice with a p38 inhibitor previously used in clinical assays causes a considerable reduction in tumor size. The study provides useful information for clinicians and pharmaceutical companies about the role of p38 in the context of colon cancer. Colorectal cancer is now the second leading cause of cancer-related death in the world.

"p38 inhibitors may have clinical applications, but probably -- and this forms part of the medicine of the future -- these will be in combination with other drugs. We are trying to find out what p38 inhibitors should be combined with to make the tumor, which is now smaller, finally disappear," explains the Spanish scientist Nebreda, head of the Signalling and Cell Cycle Lab at IRB, BBVA Foundation Cancer Research Professor and ICREA research professor.

p38 suppresses pre-tumoral stages characterized by colon inflammation

The role of p38 in cancer is not clear cut. In this same study, Indian-born Jalaj Gupta who recently obtained his PhD in Nebreda's lab and is first author of the work, demonstrates that this same protein in a pre-tumoral context, favoured by inflammation of the colon -- also known as colitis -- impedes tumor development. It is well-known that patients with chronic inflammation of the intestine, such as that caused by Crohn's disease, have a greater incidence of colon tumors that the healthy population. In order to study the relationship between inflammation and cancer, Nebreda's team use mouse models that reproduce this inflammatory context. "Given that p38 regulates inflammation and also functions as a tumor suppressor in some mouse models, our study addressed how these two functions are integrated during the colon tumorigenesis associated with inflammation," says Gupta.

An important finding of the present study is related to the contribution of p38 to the maintenance of an intact epithelial barrier, a structure that protects the intestine from toxic agents and pathogens. Mice genetically depleted of p38 in the epithelial cells that form the intestinal barrier were subjected to a cancer-inducing protocol that causes mutations and inflammation. These animals developed twice as many tumors as a group of p38-expressing mice subjected to the same protocol. The tumor-suppressing capacity of p38 has also been described in cancer of the liver and lung. "Our study highlights the complexity of p38 functions, both in cancer and in the normal maintenance of tissues, and shows why an inhibitor of this molecule could effectively have undesirable side effects. This is why it is necessary to study in depth the patients and contexts in which treatment with such inhibitors would be suitable," explains Gupta.

"All drugs currently used to treat cancer have side effects," states Nebreda, "and in this regard p38 inhibitors would be no exception. However, the administration of such inhibitors to colon cancer patients may be a useful strategy to shrink the tumor in a few days before its surgical removal." Nebreda goes on to explain that the basic research performed in his lab seeks to understand better the biology of tumor cells, the roles of the molecules involved and the mechanisms that allow tumor progression. "We try to take this basic information a step further so that it becomes clinically useful when designing new treatments," says the researcher, who joined IRB, in Barcelona, in 2010, after working in USA, UK, Germany and the CNIO in Madrid.

In collaboration with a team led by Manuel Hidalgo at the CNIO, Nebreda's group is now studying mice implanted with tumors taken from patients. The preliminary results confirm the relevance of p38 for the growth of human tumors. The researchers also have experiments underway to study the involvement of p38 in the progression of breast and lung tumors.


Story Source:

The above story is based on materials provided by Institute for Research in Biomedicine (IRB Barcelona). Note: Materials may be edited for content and length.


Journal Reference:

  1. Jalaj Gupta, Ivan del Barco Barrantes, Ana Igea, Stratigoula Sakellariou, Ioannis S. Pateras, Vassilis G. Gorgoulis, Angel R. Nebreda. Dual Function of p38α MAPK in Colon Cancer: Suppression of Colitis-Associated Tumor Initiation but Requirement for Cancer Cell Survival. Cancer Cell, 2014; DOI: 10.1016/j.ccr.2014.02.019

Cite This Page:

Institute for Research in Biomedicine (IRB Barcelona). "Key regulator of colon cancer discovered." ScienceDaily. ScienceDaily, 27 March 2014. <www.sciencedaily.com/releases/2014/03/140327123711.htm>.
Institute for Research in Biomedicine (IRB Barcelona). (2014, March 27). Key regulator of colon cancer discovered. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2014/03/140327123711.htm
Institute for Research in Biomedicine (IRB Barcelona). "Key regulator of colon cancer discovered." ScienceDaily. www.sciencedaily.com/releases/2014/03/140327123711.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) — Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) — Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) — Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) — Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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