Protein forces ovarian cancer cells to eat themselves
WEDNESDAY 19 NOVEMBER 2008
US scientists have discovered that a protein called PEA-15 halts the growth of ovarian cancer by forcing cancerous cells to digest themselves until they die - a process called autophagy or self-cannibalisation.
The cell surrounds parts of its cytoplasm - the jelly-like substance filling the cell - with membranes and then digests the contents, leaving a cavity behind. When the cytoplasm becomes riddled with these cavities, the cell dies.
Researchers at the University of Texas MD Anderson Cancer Centre analysed tumour samples from 395 women with ovarian cancer and found that the more PEA-15 protein in the tumour, the longer the patient tended to survive.
These findings provide a foundation for developing a targeted approach for ovarian cancer.
- Dr Naoto Ueno, University of Texas MD Anderson Cancer Centre
Women whose tumours contained large quantities of the protein had a average survival time of 50.2 months, compared with just 33.5 months for those with low levels of the protein.
The team also found that, in samples lacking PEA-15, the number of cancer cells was higher by 115 per cent, showing that the cells were not being destroyed by autophagy.
Senior author Dr Naoto Ueno, associate professor of breast medical oncology, commented: "These findings provide a foundation for developing a PEA-15 targeted approach for ovarian cancer and for clarifying whether this protein is a novel biomarker that can predict patient outcomes."
The study, which is published in the journal Cancer Research, revealed that PEA-15 works in two different ways depending on where it is located within the cell.
Firstly, PEA-15 blocks a protein called extracellular signalling related kinase (ERK), which fuels cancer growth from within the cell's nucleus. PEA-15 acts by binding to ERK in the nucleus and moving it into the cytoplasm where it cannot fuel cancer growth.
Secondly, it causes autophagy when located in the cell's cytoplasm.
Dr Ueno said: "These two very different actions by PEA-15 are based on the location of the protein."
The scientist concluded that the protein offers a "new dimension" for potentially targeting ERK.
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