Glioblastoma is the deadliest type of brain tumor. Cancer stem cells require 'niches' to remain viable but it is
do brain cancer cells thrive when they migrate to inhospitable sites
within the brain?
A study at The University of Texas MD Anderson Cancer Center
believes their survival may be due to deficiency of a tumor suppressor
gene called quaking (QKI), a potential new target for therapies.
Findings from the study, led by Jian Hu, assistant professor of
the Department of Cancer Biology, were published in Nature Genetics
‘A tumor suppressor gene called quaking (QKI) is a major regulator of cancer stem cells in glioblastoma.’
"Cancer stem cells require 'niches' to remain viable but it is
unclear how they survive in an environment outside of these niches both
within the same tissues or during invasion to other organs," said Hu.
"We discovered that QKI is a major regulator of these cancer stem cells
"Evidence is emerging that some brain cancer cells called glioma
stem cells possess an inexhaustible ability to self-renew and produce
tumors that resemble the features of original tumors," said Hu.
Self-renewal is a unique feature of all stem cells that creates
identical "daughter" stem cells. To maintain this ability, they must be
in a suitable environment providing them proper cellular cues. Hu's team
knew that glioma stem cells thrived when they reside in niches, such as
structures called subventricular zone, due to their ability to
"However, left unanswered is how glioma stem cells still manage to
maintain this 'stemness' when they invade and migrate from their niches
to other areas where optimal niches are less likely to be available,"
The research team believed glioma stem cells must acquire the
ability for stemness maintenance independent of their niches during
invasion and migration. Using a mouse model, they studied deletion of
major suppressing genes including QKI to see what correlation might
"Our previous studies showed that QKI is one of the tumor suppressor
genes that can potentially regulate cancer stem cells and we confirmed
this in our latest investigation," said Hu.
QKI impacted a vital cellular activity called endocytosis,
responsible for degrading the cell receptors that are essential for
maintaining stem cell self-renewal. Loss of QKI can greatly enrich the
level of these receptors and consequently enhance the self-renewal
capacity even when glioma stem cells are not in the niches. Just as a
space suit protects the astronaut from the dangers of space, a
deficiency of QKI makes the new environment safe for the transported
cancer stem cell.
"This study may lead to cancer therapeutic opportunities by
targeting the mechanisms involved in maintaining cancer stem cells,"
said Hu. "Although loss of QKI allows glioma stem cells to thrive, it
also renders certain vulnerabilities to the cancer cells. We hope to
design new therapies to target these."