Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers at IRB discover a key regulator of colon cancer


 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.

This is a picture of a colon tumor with presence of inflammatory cells (dark marks).

Credit: (Author: J Gupta, IRB)

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 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 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 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 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 colon—also known as colitis—impedes 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.


Published today in the online advanced edition of Cancer Cell and involving the participation of Vassilis Gorgoulis' group at the University of Athens, the study was started six years ago as part of the European project InflaCare, which addressed the relationship between inflammation and cancer. The study has been completed with funding from the Spanish Ministry of Economy and Competitiveness, and from an ERC Advanced Grant project awarded to Nebreda in 2012 by the European Research Council. Forthcoming research will be performed as part of the latter, which will be completed in 2017. The competitiveness of Nebreda's group at IRB is strengthened by structural funding given to the lab by the BBVA Foundation since 2011, when Nebreda was appointed a BBVA Foundation Cancer Research Professor.

Reference article:

Dual function of p38alpha MAPK in colon cancer: suppression of colitis-associated tumor initiation but requirement for cancer cell survival
Jalaj Gupta, Ivan del Barco Barrantes, Ana Igea, Stratigoula Sakellariou, Ioannis S. Pateras, Vassilis G. Gorgoulis and Angel R. Nebreda
Cancer Cell (2014)

More information:

Sònia Armengou
IRB Press Officer
+ 34 93 403 72 55/ +34 618 294 070


Founded in 2005 by the Government of Catalonia and the University of Barcelona, the Institute for Research in Biomedicine (IRB) is one of eight centres in Spain to be first recognised by the Ministry of Economy and Competitiveness as a "Severo Ochoa Centre of Excellence". The 23 groups hosted by the institute are devoted to basic and applied research at the interface between molecular and cellular biology, structural and computational biology, and chemistry, with experts in proteomics, genomics, biostatistics, and advanced digital microscopy. The research at IRB Barcelona is organised into five programmes, which work together with the common goal of conducting multidisciplinary projects that address important biomedical problems affecting our society, with special emphasis on cancer and metastasis. The institute is home to approximately 440 employees from 38 countries. IRB Barcelona's ultimate objective is to translate research results to the clinic and has already established three biotechnology spin-off companies to this end. The institute is located in the Barcelona Science Park (PCB), in the Diagonal Campus of the University of Barcelona. Director: Dr. Joan J. Guinovart. /@IRBBarcelona /

Sònia Armengou | EurekAlert!

Further reports about: BBVA Cancer Cell Foundation IRB colon discover inflammation intestine p38 tumour tumours

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>