Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Wnt Signaling Pathway - A Retrospective Look at 25 Years of Research

07.05.2008
Over the past years, biologists have gained ever deeper insights into the biochemical and molecular networks regulating the development of living beings, from the fertilized egg to complete organisms containing billions of cells and different organs.

Interestingly, only a handful of signaling pathways control this complex development. These pathways act in synergy with each other to prevent maldevelopment or tumor formation.

One of the most thoroughly researched signaling pathways is the Wnt signaling pathway, which was first characterized 25 years ago. Walter Birchmeier, a cell biologist of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch who has done important research in this field, and Alexandra Klaus, a PhD student from his research group, have written an article describing the major milestones that have substantially contributed to scientists' understanding of the Wnt signaling system. Their review has now been published in the current issue of Nature Reviews Cancer (Vol. 8, Nr. 5, pp. 387 - 398)*.

In 1982, Roel Nusse (now at Stanford University, CA, USA) and Harold Varmus (now at Memorial Sloan-Kettering Cancer Center, New York City, NY, USA) discovered Int1, the first gene of the Wnt signaling pathway. They found that this gene, when artificially activated in the mouse model, induces mammary gland tumors. At about the same time, Christiane Nüsslein-Volhard, who was later awarded the Nobel Prize and is now working at the Max Planck Institute for Developmental Biology in Tübingen, discovered that the fruit fly Drosophila melanogaster did not develop wings when the gene Wingless (Wg) was lacking. As it turned out, Int1, the mouse mammary oncogene that Nusse had discovered, was found to be identical to Wingless in Drosophila. Nusse then suggested a new nomenclature, combining Wingless (Wg) and Int1 to form the name Wnt. Since then, researchers have discovered more than 100 additional genes that play a role in the Wnt signaling pathway.

... more about:
»APC »Development »Stem »Wnt »activate »pathway »prevent

Wnt signals conserve stem cell reservoir

In the healthy cell, the Wnt signal activates a complicated signal cascade, the mechanisms of which are still not completely understood. Researchers know that the signal penetrates into the cell nucleus, the control center of the cell, and activates gene expression there. However, the Wnt signaling pathway is not only active during development from the embryo to the mature organism, but also in stem cells. Stem cells form the reservoir for replenishing those cells that are continuously turned over in the body, for example blood and skin cells. Wnt signals keep these cells from prematurely specializing into specific cells. Thus, a functioning Wnt signaling prevents the stem cell reservoir from "drying up".

Cancer due to misregulation of signaling pathways

In 1993, different researchers, including Bert Vogelstein and Kenneth Kinzler (both now at Johns Hopkins University in Baltimore, USA), discovered a link between the Wnt signaling pathway and the development of cancer. At that time, it was known that a mutation of the APC gene induces colon cancer. The new discovery, however, was that APC influences one of the key role players (ß-catenin) of the Wnt signaling pathway. Normally, the APC gene is active, ß-catenin is degraded and the Wnt signaling pathway is inhibited. However, a mutation of the APC gene prevents ß-catenin degradation. As a result, ß-catenin is able to penetrate the cell nucleus and activate certain ß-catenin genes which should be turned off in adult cells and, hence, tumors form. This process is considered to be the initial step in colon carcinogenesis.

The Wnt signaling pathway also plays a role in so-called cancer stem cells (CSCs). Many scientists suspect that tumorigenesis is associated with these cells. Cancer stem cells assume many of the characteristics of stem cells by activating programs the body used during embryonic development - for example, the Wnt signaling pathway. Jörg Hülsken, who now works at the Swiss Cancer Research Institute in Lausanne and was a former colleague of Walter Birchmeier, recently demonstrated that ß-catenin maintains the stem cell characteristics of skin cancer cells. "Since the Wnt signaling pathway does not play an important role in healthy skin cells," Walter Birchmeier said, "it might provide a possible drug target for fighting cancer stem cells."

In addition to cancer, other diseases can also develop due to a misactivation of the Wnt signaling pathway. For example, individual components of the signaling pathway can contribute to the development of heart and eye diseases, Alzheimer's disease, or schizophrenia.

"In the next 25 years, we want to identify further components of the Wnt signaling pathway and gain better insight into how these interact with each other," Alexandra Klaus explained. In the future, this research could lead to new drugs which block the Wnt signaling pathway. "However, since stem cells need this pathway, too," she pointed out, "this is not as easy as one might expect."

*Wnt signalling and its impact on development and cancer

Alexandra Klaus1 and Walter Birchmeier1

1Max Delbrück Centre for Molecular Medicine, Robert-Roessle-Strasse 10, 13,125 Berlin, Germany.

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Str. 10¸13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96; Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | idw
Further information:
http://www.mdc-berlin.de/de/news
http://www.nature.com/nrc/index.html
http://www.nature.com/nature/journal/v452/n7187/abs/nature06835.html

Further reports about: APC Development Stem Wnt activate pathway prevent

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Stretchable biofuel cells extract energy from sweat to power wearable devices

22.08.2017 | Power and Electrical Engineering

New technique to treating mitral valve diseases: First patient data

22.08.2017 | Medical Engineering

IVAM Marketing Prize recognizes convincing technology marketing for the tenth time

22.08.2017 | Awards Funding

VideoLinks
B2B-VideoLinks
More VideoLinks >>>