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How cells sense nutrients and fuel cancer cell growth
Date:10/6/2011

LA JOLLA, Calif., October 6, 2011 In cancer, genes turn on and off at the wrong times, proteins aren't folded properly, and cellular growth and proliferation get out of control. Even a cancer cell's metabolism goes haywire, as it loses the ability to appropriately sense nutrients and use them to generate energy. One particular piece of cellular machinery that is known to malfunction in a number of cancers is a group of proteins called mTORC1. This master control center coordinates many cellular functions by sensing external signals such as nutrients and growth factors and telling cells how to respond. Now, in a paper published October 7 in Molecular Cell, scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have identified a new member of the mTORC1 teama protein called p62that is crucial to the cell's response to dietary amino acids. This finding provides new information about mTORC1 and its role in cellular metabolism in both normal cells and cancer cells. What's more, it provides scientists with a new therapeutic target for cancers in which mTORC1 malfunctions.

"We think of p62 as a signaling hubit has several domains that can bind many different proteins to regulate important cellular function like growth and survival. Levels of p62 are also elevated in many cancers," said Maria Diaz-Meco, Ph.D., professor in Sanford-Burnham's NCI-designated Cancer Center and senior author of the study. "In this study, we looked for new p62 binding partners and found that p62 interacts with components of the well-known mTORC1 complex."

The amino acids a person consumes (in a high-protein diet, for example) set off a cellular chain reaction that involves mTORC1, but only some of the players in this string of events are fully understood. This study fills in some of the gaps by showing that amino acids trigger p62 to bind a protein called raptor. In turn, p62 and raptor join the mTORC1 complex. Once these and other proteins are
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Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert

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