Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


License For Cutting: How Intracellular Signaling Regulates Growth Factor Production


Cancer cells need life-essential molecules to proliferate. These growth factors are activated by ectodomain shedding of precursor proteins on the outside of plasma membrane, mainly carried out by three human cleavage enzymes. A pharmaceutical blocking of these enzymes could hinder cancer from growing but would also inhibit other life-essential processes.

Researchers from German Leibniz Institute for Age Research and Harvard University, US, showed that the factor-precursor-producing cells themselves define if cleavage may occur. This is decided by intracellular signaling. Interfering with defined signaling in cells producing cancer growth factors could lead to a new way of cancer treatment.

License for cutting: Factor-precursor-producing cells determine if and when ectodomain cleavage may occur to activate growth factors.

[Graphic: Liseth M Parra / FLI]

License for cutting: Factor-precursor-producing cells determine if and when ectodomain cleavage may occur to activate growth factors

[Graphic: K. Wagner / FLI]

As cancer cells proliferate in an unlimited way, they need to be supplied with oxygen and nutrients. For their growth and the formation of blood vessels, so-called growth factors are required. These hormone-like proteins are activated by the shedding of transmembrane precursor proteins that have to be cleaved on the outside of the plasma membrane by specialized enzymes.

In the human body, mainly three “cleavage enzymes” are responsible for ectodomain shedding of hundreds of growth factors. Hindering one of these enzymes from cleaving would certainly suppress the production of growth factors related to tumorigenesis, but would have severe side-effects: a lot of life-essential molecules would also be inhibited. Since ectodomain cleavage is highly important for homeostasis of the organism, it needs to be tightly regulated with respect to both its overall abundance and time course.

Now, in a collaborative project, researchers from German Leibniz Institute for Age Research (FLI) in Jena and renowned Harvard University in Cambridge, US, showed that obviously the precursor proteins themselves dictate if and when the “scissor”-enzymes may cut. Signal processing in the intracellular domain of the precursor-protein-producing cells is responsible for modifications that likely induce a relative positional change of the dimerization partners and, in the end, allow cleavage.

This is individually different for each precursor protein. The collaborators from Jena and Cambridge already found many details of the mechanism to explain how the intracellular domain modification communicates with the ectodomain of the substrate to allow for cleavage to occur, e.g. releasing growth factors linked to breast cancer (Epidermal Growth Factor family) and Neuregulin which is important for neuro-regeneration, as well as cleavage of a protein relevant for metastasizing of cancer cells. The latest publication in the "Journal of Biological Chemistry" now was nominated as one of the best 50 out of this year’s 6.000 publications.

“Our research results offer a new way of suppressing growth factors related to cancer cell proliferation”, Prof. Dr. Peter Herrlich, former scientific director and now associated researcher at FLI, explains. Instead of blocking the cleavage enzymes and condoning side-effects, the intracellular signal processing for single precursor proteins may be inhibited in order to specifically knock out the growth factors required by individual cancer types.

Hartmann M, Parra LM, Ruschel A, Lindner C, Morrison H, Herrlich A, Herrlich P. Inside-out Regulation of Ectodomain Cleavage of Cluster-of-Differentiation-44 (CD44) and of Neuregulin-1 Requires Substrate Dimerization. Journal of Biological Chemistry (2015), DOI 10.1074/jbc.M114.610204.

Dr. Evelyn Kästner
Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI)
Beutenbergstr. 11, D-07745 Jena
Tel.: +49 3641-656373, Fax: +49 3641-656351, E-Mail:

Background Information

The Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI) is the first German research organization dedicated to biomedical aging research since 2004. More than 330 members from over 30 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. For more information, please visit

The Leibniz Association connects 89 independent research institutions that range in focus from the natural, engineering and environmental sciences via economics, spatial and social sciences to the humanities. Leibniz Institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz Institutes collaborate intensively with universities – in the form of “WissenschaftsCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad. They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the institutes’ importance for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 18,100 individuals, including 9,200 researchers. The entire budget of all the institutes is approximately 1.64 billion EUR. See for more information.

Weitere Informationen: - Website Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI) Jena

Dr. Kerstin Wagner | idw - Informationsdienst Wissenschaft

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 >>>