March 2015
University of Kentucky Markey
Cancer Center researchers search
for Lung Cancer treatment
LEXINGTON, Ky. (Jan. 23, 2015) A new study by
–
University of Kentucky Markey Cancer Center researchers
suggests that targeting a key enzyme and its associated metabolic programming may lead to novel drug development to
treat lung cancer.
Cancer cells undergo metabolic alterations to meet the
increased energy demands that support their excess growth
and survival. The Krebs cycle in the mitochondria of cells
is used to supply both energy and building materials for cell
growth. Two mitochondrial enzymes – pyruvate carboxylase
(PC) and glutaminase replenish carbon to the Krebs cycle.
Published in the Journal of Clinical Investigation, the study
collected metabolic data directly from more than 120 human
lung cancer patients. UK’s Center for Environmental
and Systems Biochemistry (CESB) researchers
Teresa Fan, Andrew Lane, and Richard Higashi
led the study, with work done at both UK and
the University of Louisville. The researchers
worked with other collaborators to measure
the in situ activity of these two enzymes in
patients with early stage lung cancer.
When they infused the patients
with a glucose tagged with stable
heavy atoms immediately prior to
surgical removal of tumor tissue,
they found that PC was selectively
activated – in other words, PC expression
may play an important role in the development of
lung cancer.
By using molecular genetic tools to
reduce the amount of PC in human
lung cancer cells, the team observed
decreased cell growth, a compromised ability to form colonies
in soft agar (a gelatinous material specifically used to grow bacteria and other cells), and a reduced rate of tumor growth in
mice. The loss of PC also induced widespread changes in the
central metabolism of the cell, suggesting a role for PC in early
stage metabolic reprogramming.
“We now know much more about metabolic reprogramming of cancerous tissues in human patients, particularly that
the activation of pyruvate carboxylase is important to lung
cancer cell growth and survival,” s