World Cancer Day 2017: Xin Lu
World Cancer Day takes place on February 4 each year. NDM researchers are trying to understand the epidemiology and potential causes of cancer, its effect on patient lives and outcomes, as well as the basic science underpinning the unregulated cell growth that is the hallmark of the disease.
To mark World Cancer Day 2017, NDM has asked some of our cancer scientists about their research.
Professor Xin Lu is Director of the Ludwig Institute for Cancer Research, Oxford Branch. She has long standing research interests in tumour suppression and was one of the first researchers to show that the tumour suppressor p53 responds to both oncogene activation and DNA damaging signals. Her group was one of the first to demonstrate how to selectively activate p53 to kill cancer cells, through identification and characterization of the evolutionarily conserved ASPP family of proteins.
Q: How do cells change their characteristics and fate in response to external signals?
Xin Lu: The ability of cells to change their characteristics and fate in response to external signals is called cellular plasticity. This plasticity underlies cancer initiation, metastasis and resistance to therapy. There are many ways to control cell plasticity. For example, in response to what is happening outside on the cell surface, some proteins are able to move into the nucleus and change the genes that are expressed by the cell. We have been looking at a group of proteins (which we call ‘STRaND’ proteins) that shuttle into the nucleus in respond to external signals and interact with other proteins, such as transcription factors, to regulate gene expression. The changes in the gene expression program can then lead to a change in cell fate. Gene expression is a bit like a bar code that gives the cell information about how it should behave: once the cell senses what is going on outside, a different type of gene expression bar code is generated and this causes a different cell effect.
Q: How are early changes in cell fate linked to cancer in the digestive tract?
XL: Cells follow a normal ‘track’ of development and behaviour that is dependent on their normal tissue environment. But because cells are changeable and adaptable, sometimes this can go wrong. One of the early signs of disease is that the cell changes from its normal ‘track’ and sometimes this initiates cancer. In the digestive tract, stress conditions in the cell’s environment increase the risk of changes in cell fate. Stresses can happen because of infection, severe acid reflux or pH changes, and many other factors. The stress signals that the cell is exposed to lead to changes in the cell’s gene expression bar code, which can instruct the cell to behave differently; in some cases the cell can become cancerous.
We study cell plasticity at the junction between the oesophagus and the stomach. This is a junction between two types of epithelial cell layer: columnar stomach epithelium labelled here in yellow (Keratin 8); squamous oesophagus epithelium labelled here in pink (Keratin 14). In this region, cells change their characteristics in a common condition called Barrett’s oesophagus and in the cancer called oesophageal adenocarcinoma.
Q: How will understanding of the molecular basis of early changes help improve the diagnosis and treatment of cancer?
XL: It is very useful to discover the early events – or ‘molecular switches’ - that control normal cells converting into cancerous cells, as these can be used to develop new ways to diagnose cancer earlier, which makes it easier to treat cancer successfully. For example, if we can identify the different molecular bar codes that trigger the changes in cell behaviour, these could be used to help with diagnosis. In my view, the most effective way to cure cancer is to achieve early diagnosis so we can stop the cancer progressing.