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Biochem Mol biol J
ISSN: 2471-8084
Volume 3, Issue 2
Metabolomics Conference 2017
August 29-30, 2017 Prague, Czech Republic
9th International Conference and Exhibition on
Metabolomics and Systems Biology
Notes:
Page 17
Evaluating heme flux and function in lung
cancer
Li Zhang
The University of Texas at Dallas, USA
Emerging experimental data increasingly show that
despite the enhanced glycolytic flux, many types
of cancer cells exhibit intensified oxygen consumption
or mitochondrial respiration. Even under hypoxia,
cancer cells can maintain oxidative phosphorylation at
a substantial rate. Heme is a central factor in oxygen
utilization and oxidative phosphorylation. It serves as a
prosthetic group in many proteins and enzymes involved
in mitochondrial respiration. Our recent work showed that
non-small-cell lung cancer (NSCLC) cells and xenograft
tumors exhibit substantially increased levels in an array of
proteins promoting heme synthesis, uptake and function.
These proteins include the rate-limiting heme biosynthetic
enzyme ALAS, transporter proteins, and various types of
oxygen-utilizing hemoproteins, such as cytoglobin and
cytochromes. In contrast, lowering heme biosynthesis and
uptake, like inhibiting mitochondrial respiration, effectively
reduced oxygen consumption, cancer cell proliferation,
migration and colony formation. To further ascertain the
importance of elevated heme flux and function in lung
tumorigenesis, we use multiple experimental approaches
to detect the levels of heme synthesis, uptake, and
degradation in an array of NSCLC cell lines and in de
novo tumors in genetically engineered mouse models
for lung cancer. We also measure oxygen consumption
and ATP generation in these cell lines and tumors. These
experiments should reveal the degree to which elevated
heme flux—heme synthesis, uptake, and degradation—
contribute to lung tumorigenesis and how heterogeneity
in heme flux contributes to metabolic and bioenergetics
heterogeneity in lung tumors.
Biography
Li Zhang completed her PhD from UCLA and Post-doctoral studies from MIT
Department of Biology. She is the Cecil H and Ida Green Distinguished Chair
in Systems Biology Science at University of Texas at Dallas. She has worked
on studying heme signaling and function for 20+ years. She has published
many original research articles and a book entitled “Heme Biology: The Secret
Life of Heme in Regulating Diverse Biological Processes”. Her research
work has also made important contributions in understanding the roles of
molecular chaperones in cellular signaling, molecular mechanisms of oxygen
signaling, and the actions of neurotoxicants. Recently, her work focuses on
investigating heme function in lung cancer. She and colleagues have provided
a unifying view of cancer bioenergetics in a review article entitled “A Holistic
View of Cancer Bioenergetics: Mitochondrial Function and Respiration Play
Fundamental Roles in the Development and Progression of Diverse Tumors”
published in the journal Clinical and Translational Medicine.
Li Zhang, Biochem Mol biol J, 3:2
DOI: 10.21767/2471-8084-C1-002