Research by scientists at Barts and The London School of Medicine and Dentistry which identified a gene – FOXM1 - responsible for initiating human cancer, has been awarded ‘Molecule of the Year 2010’ by the International Society for Molecular and Cell Biology and Biotechnology Protocols and Research (ISMCBBPR) for its role in controlling the cell cycle in progenitor/stem-like cancer cells.
Wednesday 23 February 2011
Dr Muy-Teck Teh
This area of research is addressing some fundamental cell biological processes, and the molecule and studies around its function could have implications for the “cancer stem cell” hypothesis which is a fundamentally important, hotly debated topic for cancer biology.
In a paper published in Cancer Research last year, research led by Dr Muy-Teck Teh – a lecturer in head and neck cancer at the School’s Institute of Dentistry - showed how overexpression of Forkhead box protein M1 (FOXM1) destabilizes the cell cycle, causing the cells to grow uncontrollably towards cancer development for the first time using human cells.
In 2002, FOXM1 was first labelled an oncoprotein, a protein that could cause cancer when overexpressed. Since then, researchers have linked FOXM1 over expression to almost all types of human cancers but their limited knowledge about how the protein’s overexpression promotes cancer growth was a roadblock to the development of cancer prevention treatments.
To understand the process better, Dr Teh and his team overexpressed FOXM1 in normal adult human oral epithelial stem cells, pushing the cells toward hyperplasia, a proliferative stage that can lead to cancer.
Through this experiment, they discovered that FOXM1 interferes with the stem cell’s growth cycle and division. Normal FOXM1 levels control cell growth. When cells divide regularly, FOXM1 coordinates the division of genetic material to the two daughter cells.
However Teh’s team found that when FOXM1 is overexpressed the protein loses its control over cell growth, allowing cells to proliferate abnormally. “If you overexpress FOXM1, it could possibly disturb proper segregation of the chromosomes,” said Teh. “And this is one of the key cancer initiating events.”
FOXM1 expression is therefore becoming a popular target for the development of cancer prevention drugs. “If you get rid of FOXM1, you stop the cells from dividing,” said Teh. But elimination of the protein is not a viable option; FOXM1 is necessary for normal tissue repair and maintenance - previous groups observed that when the protein is removed from mice, pups die soon after birth from heart failure.
The problem becomes more complicated in humans who have three FOXM1 gene variants: FOXM1A, FOXM1B, and FOXM1C. These variants act as backups and could compensate when another variant malfunctions or is eliminated. The backups, however, may also predispose cells toward oncogenesis. “Most people study FOXM1B in cancer etiology,” said Teh. “But FOXM1C is also related to cancer but is less well known.” FOXM1A is inactive in normal human cells.
Teh and his team continue to investigate FOXM1’s function in the cell, hoping to understand how it instructs stem cells towards hyperplasia.
Dr Muy-Teck Teh's webpage can be found at:
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