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A Potential Sugar Fix for Tumors

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Duke Health News 919-660-1306

DURHAM, N.C. -- Researchers at the Duke School of Medicine
apparently have solved the riddle of why cancer cells like
sugar so much, and it may be a mechanism that could lead to
better cancer treatments.

Jonathan Coloff, a graduate student in Assistant Professor
Jeffrey Rathmell's laboratory in the Duke Department of
Pharmacology and Cancer Biology, has found that the tumor cells
use glucose sugar as a way to avoid programmed cell death. They
make use of a protein called Akt, which promotes glucose
metabolism, which in turn regulates a family of proteins
critical for cell survival, the researchers shared during an
April 15 presentation at the American Association of Cancer
Research Annual Meeting in San Diego.

In normal cells, growth factors regulate metabolism and cell
survival. Removing these factors leads to loss of glucose
uptake and metabolism and cell death. Cancer cells, however,
maintain glucose metabolism and resist cell death, even when
deprived of growth factors.

To study how Akt might affect these processes, Coloff and
colleagues introduced a cancer-causing form of Akt called
myrAkt, into cells that depend on growth factor to survive. The
mutant form of Akt allowed cells to maintain glucose usage and
survive even when no growth factors were present, allowing them
to bypass a normal safeguard used by cells to prevent cancer
development.

The death of normal cells after growth factors are removed
is partly accomplished by two proteins called Mcl-1 and Puma.
But the cancer-causing version of Akt prevents these two
proteins from accomplishing their tasks, allowing the cell to
survive when it shouldn't.

Once glucose was withdrawn from the environment, however,
Akt was no longer able to maintain regulation of the key
targeted proteins Mcl-1 and Puma, and the cells died.

"Akt's dependence on glucose to provide an anti-cell-death
signal could be a sign of metabolic addiction to glucose in
cancer cells, and could give us a new avenue for a metabolic
treatment of cancer," said Dr. Rathmell.

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