CANCER CELLS ADAPT ENERGY NEEDS TO SPREAD ILLNESS TO OTHER ORGANS
Want to understand why
cancer cells metastasize? Think of Sparta.
Ancient Greek warriors
were fed a special diet that better prepared them for the demands of battle on
distant fields. Cancer cells that metastasize may do the same thing according
to a new study revealing previously unknown differences between cancer cells
that continue to grow at the original tumor site, and those that travel to
other organs.
Given that a cancer
cell's unyielding ability to metastasize is the primary cause of cancer-related
death, understanding how they successfully migrate can be lifesaving.
Scientists at The
University of Texas MD Anderson Cancer Center have found that cancer cells
traveling to other sites have different energy needs from their
"stay-at-home" siblings which continue to proliferate at the original
tumor site. The study results are in the Sept. 21 online edition of Nature
Cell Biology.
The reason may lie
with the protein, PGC-1α, a type of transcription co-activator crucial to
regulation of cellular metabolism. PGC-1α appears to play a role in how cancer
cells are able to acquire unique energy sources that allow them to travel and
spread cancer in the body.
"New therapy
strategies are beginning to focus on the unique vulnerabilities of cancer cell
metabolism. Determining the metabolic requirements of invasive cancer cells
could be of therapeutic value," said Valerie LeBleu, Ph.D., assistant
professor of cancer biology at MD Anderson and lead author of the Nature Cell
Biology paper. "We found that invading cancer cells rely on mitochondria
during their transition to other cancer sites."
Cancer cells use
PGC-1α to stimulate the growth of new mitochondria, the cell's "power
plants" that generate ATP, an energy "currency" used by cells to
grow. Metastasizing cells also rely on PGC-1α for a process known as oxidative
phosphorylation that boosts ATP during the cell's journey to other sites. If mitochondria
is the kitchen, then PGC-1α is the chef, ATP the entreé and oxidative
phosphorylation a key ingredient. This overall process, mitochondria
respiration, allows some cancer cells to harness the required energy to survive
the hostile journey through tumor and normal issue, blood vessels, and entry
into new organs.
In other words, some
cancer cells are programmed to eat at home, while others have a special diet
that allows them to travel to other sites. If there was a therapeutic way to
stop the migrating cells from packing a lunch ahead of time, it could
potentially halt their journey. Suppressing PGC-1α appears to accomplish this.
"The most
dangerous cancer cells are the ones that can efficiently move and find a new
home," said Raghu Kalluri, M.D., Ph.D., chair of cancer biology and an
investigator on the study. "The study revealed a strong correlation
between PGC-1α expression in invasive cancer cells and the formation of distant
metastases in breast cancer patients."
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