Rictor protein offers scientists a new molecular target for cancer therapies

Oct 28, 2010

The discovery that a protein called Rictor plays a key role in destroying a close cousin of the AKT oncogene could provide scientists with a new molecular target for treating certain cancers, including breast cancer. Described in the September 2010 issue of the journal Molecular Cell, the study was led by scientists at Beth Israel Deaconess Medical Center (BIDMC).

The oncogenic cousin, known as SGK1, resembles the widely known AKT in structure, according to the study's senior author Wenyi Wei, PhD, of the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School (HMS).

"If we put the two proteins together, they are very similar," explains Wei. "But in one important way they are very different. AKT is stable, it lives for a long time. But SGK1 has a very short lifespan, and proteins with short lifespans tend to be powerful. Everybody's eye [has been] on AKT, but you have to wonder if this little cousin of AKT can do all the things AKT does." Wei and his team, therefore, set out to better understand how cells control SGK1.

Previous research showed that the Rictor forms a multi-protein complex called mTORC2 that activates both AKT and SGK1. Wei's team cultured cells lacking Rictor to observe the effect on SGK1. Surprisingly, they found that SGK1 levels increased.

"We said, that cannot be," notes Wei. "How could we get rid of the protein kinase that activates SGK1 and still have the SGK1 levels be heightened?"

They found their answer when they observed that the cells weren't producing more SGK1; rather, SGK1 was living longer. This suggested to the scientists that Rictor might be playing a role in the destruction of SGK1. And, in subsequent experiments, Wei found that SGK1 is indeed held in check by a protein complex made up of Rictor, Cullin-1, Rbx1, and possibly other components. The protein complex forms a cellular garbage collector called an E3 ligase that degrades SGK1 so it cannot build up.

"The protein Rictor is modular and multifunctional," said Wei. "Its function depends on its partners." This observation suggests that some proteins may act like a central machine that can work with a variety of attachments, the same way a construction vehicle can change its function depending on whether it's wielding a bulldozer or a crane. "With further study," he adds, "we may find more proteins [like Rictor] that have multiple functions. When a cell makes a protein this big, isn't it a waste of energy to have only one function?"

Wei's team further observed that once SGK1 begins to accumulate, it turns right around and interrupts the Rictor-Cullin1 complex, stifling it's garbage collection activities. "It looks like a positive feedback loop that serves to increase SGK1," says Wei.

"The novelty and significance of this work lies in the discovery of a role for Rictor in destroying SGK1, a key regulator of cell growth and cell death that is frequently associated with human cancers," said Marion Zatz, PhD, who manages cell cycle grants at the National Institutes of Health (NIH). "The finding suggests that faulty regulation of Rictor may play a part in some forms of cancer, and could offer us a new target for treating the disease."

While the exact role of SGK1 in tumor growth isn't yet clear, Wei speculates that SGK1 may play a role in by hijacking a cell's metabolism, just as its close cousin AKT does. "This mechanism we discovered may be part of what drives overexpression of SGK1," he adds.

Explore further: Bacterial immune system has a better memory than expected

Provided by Beth Israel Deaconess Medical Center

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Preventing prostate cancer the complex way

Feb 03, 2009

(PhysOrg.com) -- Blocking a specific protein complex prevents the formation of tumors in mice genetically predisposed to develop prostate cancer, researchers at the Whitehead Institute for Biomedical Research ...

An Achilles heel in cancer cells

Dec 08, 2008

A protein that shields tumor cells from cell death and exerts resistance to chemotherapy has an Achilles heel, a vulnerability that can be exploited to target and kill the very tumor cells it usually protects, researchers ...

'Bridge' protein spurs deadliest stages of breast cancer

Feb 22, 2007

A protein known for its ability to "bridge" interactions between other cellular proteins may spur metastasis in breast cancer, the disease’s deadliest stage, a study from Burnham Institute for Medical Research has found.

Recommended for you

Researchers successfully clone adult human stem cells

20 minutes ago

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

3 hours ago

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

22 hours ago

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 0

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Scientists tether lionfish to Cayman reefs

Research done by U.S. scientists in the Cayman Islands suggests that native predators can be trained to gobble up invasive lionfish that colonize regional reefs and voraciously prey on juvenile marine creatures.

Researchers develop new model of cellular movement

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

Continents may be a key feature of Super-Earths

Huge Earth-like planets that have both continents and oceans may be better at harboring extraterrestrial life than those that are water-only worlds. A new study gives hope for the possibility that many super-Earth ...

Under some LED bulbs whites aren't 'whiter than white'

For years, companies have been adding whiteners to laundry detergent, paints, plastics, paper and fabrics to make whites look "whiter than white," but now, with a switch away from incandescent and fluorescent lighting, different ...