Navigation Links
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 assembled in the lysosome (a cellular compartment where enzymes are stored), mTORC1 is activated.

One common way of determining a protein's function is to see what happens in cells that don't have it. When the team generated mice and cells that lack p62, they observed that mTORC1 no longer responded to amino acids. In other words, p62 is required for mTORC1 activation by amino acids. Moreover, it was only amino acid stimulation that required p62. Even without it, mTORC1 was still activated by other signals, such as insulin and growth factors.

"The study helps connects the dots between amino acids in the diet and downstream cellular processes like protein synthesis and cellular growth. It also shows us just how important cellular location is in the mTORC1 pathwayif the complex isn't located in the lysosome, it doesn't get activated," said Dr. Diaz-Meco. "Now we want to fill in more blanks until every step in this pathway is completely understood. This information will allow us to better understand cellular metabolism and its link to human diseases such as cancer."

This finding is the result of a long-time collaboration with the laboratory of another Sanford-Burnham professor, Jorge Moscat, Ph.D. The laboratories of Dr. Diaz-Meco and Dr. Moscat have been unraveling the roles and functions of p62 since they first discovered it in 1998, as part of a complex network of proteins that play critical roles in the control of obesity and inflammation in cancer. These investigators believe that this network is a fertile ground for new therapeutic targets for obesity and type 2 diabetes, as well as cancer. Projects underway in their labs are aimed at pharmacologically targeting p62 and related proteins to generate new medicines for these diseases. This particular study, now published in Molecular Cell, also involved contributions from two other Sanford-Burnham faculty members, Angeles Duran, Ph.D. and Malene Hansen, Ph.D.


'/>"/>

Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert

Related medicine news :

1. Rebooting the system: Immune cells repair damaged lung tissues after flu infection
2. Correcting sickle cell disease with stem cells
3. Louisiana State University Health Sciences Center research discovers key to survival of brain cells
4. How normal cells become brain cancers
5. Gene may be good target for tough-to-kill prostate cancer cells
6. New UC research promises better collection of prostate cancer cells
7. Scientists shut down pump action to break breast cancer cells drug resistance
8. Cell Transplantation study shows bone growth from implanted tooth and dental pulp stem cells
9. Virus kills breast cancer cells in laboratory
10. Researchers discover how promiscuous parasites hijack host immune cells
11. Stem cells, potential source of cancer-fighting T cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/3/2016)... ... 03, 2016 , ... In April, Amerec launched a new website designed with ... the best steam and sauna solutions. , First, the Amerec website has been redesigned ... all of the site’s features, especially the Steam Builder Tool , to both ...
(Date:5/3/2016)... ... 2016 , ... California health startup Pegara announced today the ... assess their risk of developing Alzheimer’s disease. Using a questionnaire based on years ... Score™” that summarizes how their lifestyle choices may affect their chances of developing ...
(Date:5/3/2016)... ... May 03, 2016 , ... Horizon Blue Cross Blue ... as one of the nation’s most accomplished business technology innovators by InformationWeek, earning ... recognition for technology achievements that have enabled the delivery of the company’s innovative ...
(Date:5/3/2016)... ... May 03, 2016 , ... Excessive panting in the car or cowering ... "Pet owners often think anxiety only manifests itself as trembling or ‘tail between the ... there’s things that be done about it,” says Dr. Jim Lowe, technical services veterinarian ...
(Date:5/3/2016)... ... May 03, 2016 , ... Nationally recognized personal injury law firm Monge & Associates ... roses to anyone who wants one for their Mother or any other mother figure. , ... contributions of Mothers.” Monge goes on to say, “we are choosing to do this ...
Breaking Medicine News(10 mins):
(Date:5/3/2016)... , May 3, 2016 ... Research Report provides a basic overview of the ... post which the surgical mesh report explores into ... Complete report on Surgical Mesh market ... and 98 tables and figures is available at ...
(Date:5/2/2016)... , May 2, 2016  Deerfield announced today ... of Graybug Vision, Inc. Graybug Vision is an ... that may transform care for ocular diseases including ... Vision,s technology was first developed at Johns Hopkins ... startup venture. Graybug Vision is ...
(Date:4/29/2016)... , April 29, 2016  In the next ... to shift from systems dependent on CRTs monitors to ... of modality CRT Medical monitors and will automatically ... a host of foreseeable benefits to this technological ... existing modalities have to be replaced in order ...
Breaking Medicine Technology: