By Jason Bardi | February 22, 2012
Uncovering the network of genes regulated by a crucial molecule involved in cancer called mTOR, which controls protein production inside cells, researchers at the University of California, San Francisco (UCSF) have discovered how a protein “master regulator” goes awry, leading to metastasis, the fatal step of cancer.
Their work also pinpoints why past drugs that target mTOR have failed in clinical trials, and suggests that a new class of drugs now in trials may be more effective for the lethal form of prostate cancer for which presently there is no cure.
Described this week in the journal Nature, the protein mTOR is a “master regulator” of human protein synthesis. It helps normal cells sense nutrients and control cell growth and metabolism. But in many forms of cancer, this process goes awry, and mTOR reprograms normal cells to aberrantly divide, invade and metastasize.
“Many human cancers show hyperactivation of this pathway,” said Davide Ruggero, PhD, an associate professor of urology and member of the Helen Diller Family Comprehensive Cancer Center and the Multiple Myeloma Translational Initiative at UCSF. “Until now, we have not known how hyperactive mTOR perturbs the synthesis of certain proteins leading to fatal cancer.”
In the human body, mTOR is a molecular sensor that helps cells respond to favorable or unfavorable environments. Under ordinary conditions, it acts as a master regulator of genes that induce cells to growth and divide. In times of scarcity, when somebody is starving for instance, mTOR shuts down much of the machinery that makes proteins so that an organism can conserve energy.
In cancer, this careful balance is lost. The rogue mTOR protein goes haywire and signals tumor cells to become bigger to divide, undergo metastasis and invade new, healthy tissues. Metastasis is the primary cause of cancer patient death.
“We are now discovering that during tumor formation mTOR leads to metastasis by altering the synthesis of a specific group of proteins that make the cancer cells move and invade normal organs,” Ruggero said.