Free Newsletters - Space - Defense - Environment - Energy
. Farming News .

Targeting cancer's sweet tooth
by Staff Writers
New York NY (SPX) Oct 24, 2013

File image.

Ludwig researchers have elucidated a key mechanism by which cancer cells change how they metabolize glucose to generate the energy and raw materials required to sustain runaway growth.

Published online in Cell Metabolism, the Ludwig Cancer Research study also reveals how the aggressive brain cancer glioblastoma harnesses the mechanism to resist targeted therapies that should disrupt this capability-known as the Warburg effect-and suggests how such resistance might be overcome. In detailing the molecular circuitry of the phenomenon, the researchers uncover several possible targets for new drugs that might disrupt cancer cell metabolism to destroy tumors.

"Cancer and other fast-growing cells extract energy from glucose using a process that ordinarily kicks in only when oxygen is in short supply," explains Ludwig scientist Paul Mischel, MD, who is based at the University of California, San Diego School of Medicine.

"This allows them to thread the needle: they get the energy they need from glucose but also retain the carbon-based building blocks for molecules like lipids, proteins and DNA, which dividing cells need in large quantities."

Until recently, relatively little was known about the biochemical circuits that induce this vital metabolic shift in cancer cells. Earlier this year, however, Mischel and his colleagues published a study describing how an aberrant growth signal found in many glioblastomas is channeled to induce the Warburg effect.

That signaling cascade, which involves the key proteins PI3 kinase (PI3K), Akt and mTORC1, culminates in the activation of a transcription factor-a controller of gene expression-named c-Myc. "In many cancer cells," says Mischel, "c-Myc seems to be a lever that links growth signaling pathways with the machinery that controls the uptake and use of nutrients."

In the current study, Mischel, who did the research in collaboration with Ludwig researchers Kenta Masui, MD, PhD and Web Cavenee, PhD, both also at UC San Diego, identifies a second interacting biochemical cascade that is independent of the PI3K-Akt-mTORC1 signal and uses distinct biochemical circuits and an unusual mechanism to turn on c-Myc.

This pathway, Mischel and his colleagues report, depends on signals from a protein complex named mTORC2. The researchers show that when mTORC2 is switched on, it silences two other transcription factors, FoxO1 and FoxO3, which would otherwise suppress the activation of c-Myc in the nucleus of the cell. Further, they learned that the silencing of the FoxOs occurs through a chemical modification-known as acetylation-a process that has not been well understood.

The study has significant implications for cancer therapy. "Many drugs have recently been devised to block PI3K-Akt-mTORC1 signaling," explains Mischel.

"What we show is that when you use those drugs, you will probably drive the acetylation of the FoxOs through mTORC2, and inadvertently fuel the Warburg effect. In other words, this new pathway is likely to be responsible for resistance to those drugs. Our data suggest that to disrupt the Warburg effect and kill cancer cells, you have to develop therapies that target both signaling pathways. That's the main clinical ramification of this finding."

Mischel and his colleagues find that glioblastomas that rely predominantly on the mTORC2-mediated pathway tend to have the worse prognosis. Further, their studies suggest that lung cancer cells, too, use this pathway to induce the Warburg effect.

"Increasingly," says Mischel, "we're using glioblastoma as a system to understand a variety of other cancers and, in fact, this finding has broader relevance because the signaling pathways identified here are conserved across cancer types." Different cancers, he explains, are fueled by different types of mutations to growth factor receptors, but the signals these mutated receptors transmit tend to converge on a subset of signaling proteins.

"Our identification of the key molecules-and novel signaling mechanisms-involved in this pathway, has opened up a landscape rich in possible targets for novel cancer drugs," says Mischel. His laboratory, he says, is now working with other Ludwig researchers to identify small drug-like molecules that might disrupt key steps of the mTORC2-mediated pathway.


Related Links
Ludwig Institute for Cancer Research
Farming Today - Suppliers and Technology

Comment on this article via your Facebook, Yahoo, AOL, Hotmail login.

Share this article via these popular social media networks DiggDigg RedditReddit GoogleGoogle

Memory Foam Mattress Review
Newsletters :: SpaceDaily :: SpaceWar :: TerraDaily :: Energy Daily
XML Feeds :: Space News :: Earth News :: War News :: Solar Energy News

To swallow or to spit? New medicines for llamas and alpacas
Vienna, Austria (SPX) Oct 24, 2013
Llamas and alpacas are becoming increasingly popular in Europe and are highly appreciated as trekking animals and as sources of wool. Although they are robust, they occasionally fall ill but there are no authorized drugs for the species on the market. Researchers at the University of Veterinary Medicine Vienna (Vetmeduni Vienna) have developed an oral "paste" that can be mixed with drugs a ... read more

New evidence on lightning strikes

How Earth's rotation affects vortices in nature

Tiny drones create new, highly detailed mapping of Matterhorn

Satellites proposed as way to bring early detection of wildfires

Software Uses Cyborg Swarm To Map Unknown Environs

DLR, Thales Alenia Space and SES Develop Innovative Space-Based Air Traffic Control Monitoring System

Boeing, China Southern and China Aviation Authorities Establish Precision Navigation Procedures

Plan maps development of China's sat-nav industry

Risk of Amazon rainforest dieback is higher than IPCC projects

Economic Assessment of Mountain Pine Beetle Timber Salvage

Without plants, Earth would cook under billions of tons of additional carbon

A few tree species dominate Amazon

The potential of straw for the energy mix has been underestimated

Scientists Identify Key Genes for Increasing Oil Content in Plant Leaves

Ethanol Safety Seminar Planned in Tacoma

US Biodiesel Production Surpasses Set Target for Second Straight Year

Solar panels can be used to provide heating and air conditioning

Cleaner and greener cities with integrated transparent solar cells

Simpler Manufacturing Cuts Cost Of Organic-Inorganic Hybrid Solarcells

New NRDC Crowdfunding Campaign to Connect Schools to Solar Power

Spain launches first offshore wind turbine

Key German lawmaker: End renewable energy subsidies by 2020

Installation of the first AREVA turbines at Trianel Windpark Borkum and Global Tech 1

Trump's suit to halt wind farm project to be heard in November

Two China miners saved 10 days after flood, 10 confirmed dead

Calculating the true cost of a ton of mountaintop coal

Ukraine designates 45 coal mines for sale in privatization push

German coal mine turns village into ghost town

China paper's front-page demand for journalist release

China paper's front-page demand for journalist release

Chinese villagers clash with police, injuring 27: reports

Outspoken China professor fired for poor teaching: university

The content herein, unless otherwise known to be public domain, are Copyright 1995-2014 - Space Media Network. AFP, UPI and IANS news wire stories are copyright Agence France-Presse, United Press International and Indo-Asia News Service. ESA Portal Reports are copyright European Space Agency. All NASA sourced material is public domain. Additional copyrights may apply in whole or part to other bona fide parties. Advertising does not imply endorsement,agreement or approval of any opinions, statements or information provided by Space Media Network on any Web page published or hosted by Space Media Network. Privacy Statement