Navigation Links
Researchers at IRB discover a key regulator of colon cancer
Date:3/27/2014

Barcelona, Thursday 27 March 2014.- 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 tumour development. Intriguingly, on the other hand, once a tumour has formed, p38 is required for the survival and proliferation of colon cancer cells, thus favouring tumour 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 familymolecules 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 tumour 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 tumour 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 probablyand this forms part of the medicine of the futurethese will be in combination with other drugs. We are trying to find out what p38 inhibitors should be combined with to make the tumour, 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 colonalso known as colitisimpedes tumour 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 tumours 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 tumour 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 tumours as a group of p38-expressing mice subjected to the same protocol. The tumour-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 tumour 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 tumour cells, the roles of the molecules involved and the mechanisms that allow tumour 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 tumours taken from patients. The preliminary results confirm the relevance of p38 for the growth of human tumours. The researchers also have experiments underway to study the involvement of p38 in the progression of breast and lung tumours.


'/>"/>

Contact: Sònia Armengou
armengou@irbbarcelona.org
34-934-037-255
Institute for Research in Biomedicine (IRB Barcelona)
Source:Eurekalert  

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
3. Researchers attempt to solve problems of antibiotic resistance and bee deaths in one
4. UNH researchers find African farmers need better climate change data to improve farming practices
5. Ottawa researchers to lead world-first clinical trial of stem cell therapy for septic shock
6. Researchers uncover molecular pathway through which common yeast becomes fungal pathogen
7. Researchers print live cells with a standard inkjet printer
8. Columbia Engineering and Penn researchers increase speed of single-molecule measurements
9. Researchers reveal how a single gene mutation leads to uncontrolled obesity
10. Researchers discover novel therapy for Crohns disease
11. New paper by Notre Dame researchers describes method for cleaning up nuclear waste
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers at IRB discover a key regulator of colon cancer
(Date:4/15/2016)...  A new partnership announced today will help ... in a fraction of the time it takes ... life insurance policies to consumers without requiring inconvenient ... Diagnostics, rapid testing (A1C, Cotinine and HIV) and ... weight, pulse, BMI, and activity data) available at ...
(Date:4/13/2016)... April 13, 2016  IMPOWER physicians supporting Medicaid patients ... a new clinical standard in telehealth thanks to a ... the higi platform, IMPOWER patients can routinely track key ... body mass index, and, when they opt in, share ... visit to a local retail location at no cost. ...
(Date:3/29/2016)... 29, 2016 LegacyXChange, Inc. (OTC: ... and SelectaDNA/CSI Protect are pleased to announce our successful ... a variety of writing instruments, ensuring athletes signatures against ... collectibles from athletes on LegacyXChange will be assured of ... DNA. Bill Bollander , CEO states, ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016 Houston Methodist Willowbrook ... Cy-Fair Sports Association to serve as their official ... Houston Methodist Willowbrook will provide sponsorship support, athletic ... with association coaches, volunteers, athletes and families. ... Cy-Fair Sports Association and to bring Houston Methodist ...
(Date:6/23/2016)...  The Biodesign Challenge (BDC), a university competition that ... living systems and biotechnology, announced its winning teams at ... New York City . The teams, ... at MoMA,s Celeste Bartos Theater during the daylong summit. ... curator of architecture and design, and Suzanne Lee ...
(Date:6/23/2016)... , ... June 23, 2016 , ... STACS DNA Inc., ... Leader at the Arkansas State Crime Laboratory, has joined STACS DNA as a Field ... DNA team,” said Jocelyn Tremblay, President and COO of STACS DNA. “In further expanding ...
(Date:6/23/2016)... , June 23, 2016  Blueprint Bio, a company ... to the medical community, has closed its Series A ... Nunez . "We have received a commitment ... capital we need to meet our current goals," stated ... us the runway to complete validation on the current ...
Breaking Biology Technology: