Francis Crick Institute scientists have discovered that a gene
in fruit flies called 'spidey' regulates a key lipid-metabolising
enzyme involved in cell growth and proliferation.
Alex Gould of the Crick, who led a team including scientists at
the University of Nevada, says: "Our findings used the power of
fruit fly genetics to identify a new regulator of the
lipid-metabolising enzyme phosphoinositide 3-kinase (PI3K). PI3K is
an important enzyme as it drives the growth and proliferation of
many types of cells including cancer cells."
Lipids play many important roles in a cell. They are a major
part of the membrane surrounding a cell, they provide fuel for
metabolism and they also serve as signals that regulate cell
behaviour.
The PI3K enzyme synthesizes a class of lipids known as
phosphatidylinositides, which act as signals that stimulate cell
growth, proliferation and metabolism.
The researchers found that the fruit fly gene spidey is
important for keeping the brake on PI3K, thus preventing it from
driving the inappropriate overgrowth of liver-like cells called
oenocytes.
Given that many cancer cells are dependent on metabolic pathways
for survival, optimising new drugs that inhibit the PI3K pathway is
a promising approach for treating tumours and has already led to
several clinical trials.
Dr Gould emphasise that future research is needed to determine
whether the work in fruit flies will translate into humans, which
also have spidey-like genes. "If so, and right now it is a big if,
spidey-like genes might be suitable new targets for anti-cancer
therapies aimed at switching off PI3K and thus the growth of
tumours," he says.
To identify spidey and other new regulators of the PI3K pathway
in fruit flies, Einat Cinnamon and other members of the team used
RNA interference (RNAi) - an experimental method that is used to
turn off the expression of specific genes. With the help of RNAi
and other sophisticated genetic tools available in fruit flies,
they could examine the effects of switching off genes in a specific
tissue at a specific stage of the life cycle.
The paper, Drosophila Spidey/Kar Regulates Oenocyte
Growth via PI3-Kinase Signaling, is published in PLoS
Genetics.