Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Scientists find molecular pathway suspected in precancerous stomach lesions


May lead to improved diagnosis and prevention of stomach-esophagus cancer

Researchers at Dana-Farber Cancer Institute have identified a chain of molecular signals that generate the specialized lining of the stomach during fetal development – a discovery that could lead to better diagnosis, treatment and prevention of stomach and esophageal cancer in adults.

Damage to the stomach lining, such as from acid reflux or helicobacter pylori (H. pylori) infections, might reactivate the newly found signaling pathway – but in this situation it would work in the opposite direction. As a result, the lining reverts to a more generic intestinal type of cells that form cancer-prone lesions.

Ramesh Shivdasani, MD, PhD, of Dana-Farber, senior author of a report in the April 4 issue of Developmental Cell, said the finding "opens a window that could help us eventually interfere with these pathways when they become abnormal. It should give us a list of potential therapeutic targets and could even help us to prevent the development of the precancerous lesions."

The lead author is Byeong-Moo Kim, PhD, also of Dana-Farber.

Patients with the increasingly common disorder known as Gastroesophageal Reflux Disease, or GERD, are at risk of developing precancerous lesions in the upper end of the stomach or the adjoining lower end of the esophagus. These lesions require intense frequent monitoring by endoscopy and sometimes prophylactic surgery to decrease the threat of this dangerous form of cancer. Cancer of the "gastroesophageal junction" has increased dramatically in the past two decades, especially in patients younger than 40 years.

Shivdasani’s laboratory studies the "rules" according to which body tissues develop their distinctive form and function at the beginning of life, because they may be reactivated, abnormally, when cancer arises later.

"Cancers of the stomach are almost always preceded by the conversion of the stomach type of lining to an intestinal type," says Shivdasani. In the developing fetus, the entire digestive tract is initially lined with intestinal-type cells. At a certain point, the activation of a molecular signaling pathway causes this layer to become more specialized, or differentiated, for the lining of the stomach and esophagus. Thereafter, the pathway falls silent, unless, many years later, damage to the lining sets it in motion again.

In the mouse fetus, the differentiation of intestinal lining into stomach lining happens rapidly, during a window of only one day, around the 12th and 13th days of gestation. (The corresponding period in the human fetus is during the 8th to 10th weeks.)

"We found that the epithelium [lining layer] is malleable, and depends completely on this pathway to instruct it to become stomach," says Shivdasani. "In the absence of this pathway, the epithelium would develop into the default intestinal state."

In experiments in mice, and with cultured mouse stomach and intestinal tissue, the scientists demonstrated that the signals that drive the differentiation of stomach lining are sent by a layer of cells, known as mesenchyme, that lie directly beneath the intestinal lining. The key player in the signaling pathway, they found, is a transcription factor – a protein that governs the expression of genes under its control – called Barx1. The main action of Barx1 in stomach lining formation is to block signaling through another pathway known as Wnt, the scientists found.

"Barx1 gives us a handle on what elements of the pathway might allow the stomach to differentiate abnormally into intestine as a result of injury to the stomach lining, setting the stage for cancer," Shivdasani says.

"These research findings offer the hope of identifying a protein marker that can be used to screen for these diseases and even to serve as a target for newly designed forms of therapy," said Robert Mayer, MD, director of Dana-Farber’s Center for Gastrointestinal Oncology, who was not involved in the study.

Bill Schaller | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

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 >>>