Scientists have shown that the tumour suppressor gene TP53 and genes in TOR family play a role in fat production during normal cell division, with important implications for cancer biology.
The study revealed that the ‘timer’ that controls cell cycle division also controls the synthesis of essential fats, also known as lipids, in order to coordinate growth.
Lipids are important building blocks for all cells. They form a membrane around cells, and create compartments within cells that have different functions. When a cell divides, it needs twice as much lipid material in order to form a new daughter cell that is identical to its parent.
Until now it had not been clear at what point cells produce more lipids ahead of cell division, or how this process is controlled.
Researchers from The Institute of Cancer Research, London, performed an RNAi screen in fruit fly cells to look for genes that affect the activity of a key fat-regulating enzyme called IRE1-XBP1.
Based on results from this screen, researchers found that new lipids are made during the S and G2 phases of the cell cycle, after they have committed to undergoing cell division.
The tumour suppressor gene TP53 was found to have a role in regulating lipid production, meaning it is critical in preventing ‘structural’, as well as genetic, errors in new cells – stalling the cell cycle to ensure there are enough lipid building blocks to construct a new cell.
This work also revealed that genes in the TOR molecular signalling pathway – which are implicated in the development of some cancers – including the transcription factor SREBP, seemed to have a role in controlling lipid production during the cell cycle. In particular, TORC1 was found to promote lipid production by slowing down progression of the cell cycle.
Finally, the researchers showed that the hormone insulin plays a role in both the cell cycle and fat production by activating TORC1 and slowing down the cell cycle timer so that cells have longer to produce lipid building blocks necessary for cell division and growth.
Dr Chris Bakal, Team Leader in Dynamic Cell Systems at the ICR, said:
“Our study explains how cells ensure they have the right amount of fat throughout their life cycle. Lipids are essential building blocks of all cells. We have shown how manufacture of new lipids is kept on hold when the cell is not dividing, but is elegantly linked to the same ‘timer’ that controls cell division. This means lipid production is switched on at a critical time in the cell cycle allowing the cell to produce enough fat to create healthy daughter cells. Cancer genes, such as p53 and those involved in the TOR pathway, are critical to regulate these processes.
“Now we better understand this how the cell controls lipid production, we can ask what is happening to this process in cancer. Cancer cells need to divide rapidly, so in future we will be asking how they regulate their fat production. If we could find a way to interfere with this process it may be a way to target cancer cells.”
The paper was published in Open Biology and was funded by the BBSRC and Cancer Research UK.