‘Spidey’ genes that regulate cell growth discovered in fruit flies

‘Spidey’ genes
Liver-like cells in the fruit fly©  Credit: Annick Sawala and Alex Gould.

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.