Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stopping the clock: Genetics of tumor latency in skin cancer

23.01.2006


Dr. Anthony E. Oro and colleagues (Stanford University) have identified two key Gli protein degradation signals that directly affect tumor latency in a mouse model of human skin cancer.



Their paper has been made available online ahead of print and will appear on the cover of the February 1 issue of the scientific journal Genes & Development.

Gli proteins are transcriptional mediators of the Sonic Hedgehog intracellular signaling pathway. Aberrant Shh signaling is implicated in a variety of human birth defects and about 25% of human tumors. Dr. Oro and colleagues found two sequences in the Gli1 protein – called Dn and Dc – that are recognized by the proteasome and facilitate Gli protein destruction. Mutations in these sequences (or "degrons" as they are called) prevent Gli1 degradation, causing, rather, the Gli1 protein to accumulate, and lead to accelerated tumorigenesis.


"Although we knew inducing hedgehog signaling in cells played an important role in human cancer induction and maintenance, we were puzzled by why it took so long in many cases. We were excited to find that normal cells have a way of protecting themselves from too much of the active Gli protein and surprised to discover that cancer cells appear to have disarmed that ability."

Dr. Oro and colleagues used transgenic mice expressing various forms of the Gli1 protein to demonstrate the link between Gli1 accumulation and tumor latency. Transgenic mice expressing wild-type Gli1 (in which the degrons are completely intact) develop basal cell carcinoma (BCC)-like tumor 6-8 weeks after birth. Mice expressing an altered form of either Dn or Dc (in which Gli1 is partially stabilized) develop BCC-like lesions at an earlier age. Remarkably, mice with mutated forms of both degrons (in which Gli1 is not degraded by the proteasome) die at birth, presenting severe ulcerating skin lesions similar to human BCCs.

This work convincingly shows that Gli protein accumulation contributes to the latency of Shh-dependent tumor formation, and that the modulation of Gli protein stability may thus represent a novel anticancer therapy. "We hope our studies will lead to ways to enhance the cell’s ability to get rid of Gli and halt cancer development," adds Dr. Oro.

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.edu

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

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

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

Construction of practical quantum computers radically simplified

05.12.2016 | Information Technology

NASA's AIM observes early noctilucent ice clouds over Antarctica

05.12.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>