Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein That Promotes Cancer Cell Growth Identified

28.07.2009
Scientists at Burnham Institute for Medical Research (Burnham) have found that the Caspase-8 protein, long known to play a major role in promoting programmed cell death (apoptosis), helps relay signals that can cause cancer cells to proliferate, migrate and invade surrounding tissues. The study was published in the journal Cancer Research on June 15.

The team of scientists, led by Kristiina Vuori, M.D., Ph.D., professor and director of the Cancer Center at Burnham, showed that Caspase-8 caused neuroblastoma cancer cells to proliferate and migrate. For the first time, Caspase-8 was shown to play a key role in relaying the growth signals from epidermal growth factor (EGF) that cause cell division and invasion.

The researchers also identified an RXDLL amino acid motif that controls the signaling from the EGF receptor through the protein kinase Src to the master cell proliferation regulator protein, MAPK. This same signaling pathway stimulates neuroblastoma cells to migrate and invade neighboring tissues--a critical process in cancer metastasis.

“Caspase-8 has a well defined role in promoting apoptosis, especially in response to activation of the so-called death receptors on the outside of cells,” said Darren Finlay, Ph.D., first author on the paper. “Although Caspase-8 is involved in apoptosis, it is rarely deleted or silenced in tumors, suggesting that it was giving cancer cells a leg up in some other way. Our studies suggest that Caspase-8 does so by activating the MAPK pathway through Src.”

Using immuno-blot assays, the scientists showed that EGF signaling was absent in a cancer cell line that is deficient in Caspase-8 and that EGF signaling can be restored by reconstituting the cells with wildtype Caspase-8. Sequence homology studies helped to identify a RXDLL motif in the protein, a sequence that has been shown in other proteins to function in cell signaling. The researchers also used immune-blot assays to demonstrate that reconstituting the Caspase-8 deficient cells with Caspase-8 with mutations in the RXDLL domain did not result in EGF signaling. This suggests that Caspase-8 mediates signaling through the RXDLL domain. The scientists had previously shown in another study that Caspase-8 associates with Src, a protein known to be involved in cancer cell proliferation. In this study they showed that interruption in this association disrupts EGF signaling indicating that Caspase-8 exerts EGF signaling through Src.

Cancer results from excessive cell division and reduced cell death. A number of cell death proteins are missing from human tumors, allowing cancer cells to ignore the cues that keep their growth in check. Cells that can evade apoptosis have a clear growth advantage. Because Caspase-8 is involved in programmed cell death, it would seem that reducing Caspase-8 in cancer cells would provide a growth advantage. However, this is rarely observed in human cancers.

By providing a more complete understanding of the molecular mechanisms involved in cancer cell proliferation and migration, these results point to Caspase-8 as a novel therapeutic intervention point for treating multiple types of human cancers.

About Burnham Institute for Medical Research
Burnham Institute for Medical Research is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country.

The institute ranks among the top four institutions nationally for NIH grant funding and among the top 25 organizations worldwide for its research impact. For the past decade (1999-2009), Burnham ranked first worldwide in the fields of biology and biochemistry for the impact of its research publications (defined by citations per publication), according to the Institute for Scientific Information.

Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit public benefit corporation.

Josh Baxt | Newswise Science News
Further information:
http://www.burnham.org

More articles from Life Sciences:

nachricht Cloud Formation: How Feldspar Acts as Ice Nucleus
09.12.2016 | Karlsruher Institut für Technologie

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>