Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Global signaling study suggests cancer link to protein promiscuity

17.11.2005


Haphazard activation of secondary signaling pathways may fuel cancer’s genesis



When found at abnormally high concentrations, two proteins implicated in many human cancers have the potential to spur indiscriminate biochemical signaling inside cells, chemists at Harvard University have found. Their finding may expand scientists’ current understanding of oncogenesis -- that cancer arises when an oncoprotein becomes overactive, ramping up the biochemical pathways that it normally activates -- suggesting that an important additional mechanism could be the inappropriate activation of numerous secondary pathways.

"Our data offer a new way to think about cancer, adding to the current paradigm," says Gavin MacBeath, an assistant professor of chemistry and chemical biology in Harvard’s Faculty of Arts and Sciences and co-author of a paper published in the journal Nature. "We present the hypothesis that an important component of oncogenesis is the ability of proteins to turn on alternative, secondary signaling pathways when overexpressed, rather than simply upregulating primary pathways."


MacBeath and colleagues studied the four human ErbB receptors, which set in motion widely studied cellular processes including cell migration, adhesion, growth and death. These receptors span the cell membrane; the external portion binds free growth factors, creating biochemical signals propagated inside the cell.

Each ErbB receptor has multiple intracellular binding sites where proteins can dock, but MacBeath’s group found that only two of the four ErbB proteins, known as EGFR and ErbB2, become dramatically more "promiscuous" -- able to recruit and activate a large number of different signaling proteins -- when present at high concentrations.

"These two promiscuous ErbB proteins are known to be overactive in many human cancers, suggesting that their ability to turn on rampant signaling may contribute to their high oncogenic potential," MacBeath says. "This newfound link may also offer alternative strategies for therapeutic intervention. Many of today’s cancer pharmaceuticals work by targeting individual receptors such as EGFR and ErbB2. Our work suggests that new drugs could target critical secondary pathways that are inappropriately activated by promiscuous proteins."

The researchers studied interactions between signaling proteins and the ErbB receptors using a protein microarray technique developed by MacBeath in 2000, when he was a research fellow in Harvard’s Bauer Center for Genomic Research. This method can rapidly and simultaneously assess the strength of interactions among tens of thousands of proteins genome-wide. The current research analyzed the interactions between 159 proteins and 33 binding sites on the four ErbB receptors. The scientists looked not only at whether a given protein-receptor pair interacted, but also how strongly.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Studies and Analyses:

nachricht Some brain tumors may respond to immunotherapy, new study suggests
11.12.2018 | Columbia University Irving Medical Center

nachricht Climate change and air pollution damaging health and causing millions of premature deaths
30.11.2018 | International Institute for Applied Systems Analysis (IIASA)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Magic number colloidal clusters

13.12.2018 | Life Sciences

UNLV study unlocks clues to how planets form

13.12.2018 | Physics and Astronomy

Live from the ocean research vessel Atlantis

13.12.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>