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Unexpected role: EGFR protects cancer cells from starving
Date:5/5/2008

HOUSTON - A growth factor receptor found abundantly on the surface of cancer cells and long known to fuel cancer growth also protects tumor cells from starvation by a newly identified mechanism, researchers at The University of Texas M. D. Anderson Cancer Center report in the May 5 issue of Cancer Cell.

The epidermal growth factor receptor (EGFR) stabilizes another cell membrane protein that channels a constant supply of glucose to cancer cells, saving them from devouring themselves, a team led by Isaiah J. Fidler, D.V.M., Ph.D., professor and chair of M. D. Anderson's Department of Cancer Biology, and Mien-Chie Hung, Ph.D., professor and chair of the department of Molecular and Cellular Oncology.

Their findings could explain why some drugs that target what was previously thought to be EGFR's only role in cancer proliferation have had limited success in patients. Drugs that block EGFR's activation by growth factors - its tyrosine kinase activity -- have gotten response rates in 10 percent to 20 percent of patients across a variety of cancers.

"We show that the receptor is active independent of its kinase activity," Fidler said. "Up until now everyone - including us - focused on kinase, kinase, kinase."

The team shows that EGFR binds to another cell membrane protein called the sodium/glucose co-transporter (SGLT1), protecting SGLT1 from destruction by the cell's proteasome complex, Hung noted. "This complex stabilizes SGLT1 so it continues to transport glucose from the cell membrane into the cell," Hung said.

A "terrific target"

Cancer cells have a high metabolic rate and require more glucose to fuel their activities than do normal cells, Fidler said.

"Inhibiting the kinase activity of the receptor does not interfere with EGFR stabilizing SGLT1, allowing cancer cells to maintain intracellular glucose levels," Fidler said. "To destroy tumor cells by depriving them of glucose one n
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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