Alana Cutliffe and Dr John Mackrill

When dissolved in water, calcium forms calcium ions (Ca2+). Inside cells, Ca2+ acts as a key signal, controlling almost every process from movement, to metabolism and the expression of genes. However, excessively high concentrations of Ca2+ lead to cell death [1].
Worldwide, oesophageal cancer (OEC) is the sixth leading cause of cancer-related mortality and is poorly responsive to treatment [2]. OEC cells respond to changes in their environment, including alterations in acidity, with rises in intracellular Ca2+. Increased Ca2+ in OEC cell Ca2+ damages the DNA [3] and causes inflammation [4], both of which promote the development and progression of cancer. Little is known about which molecular mechanisms underlie these changes in Ca2+, but probably include pumps, (which increase the amount of Ca2+ within certain compartments of the cell) and channels (which are like “valves”) Consequently, our short-term aim is to identify which molecular mechanisms are involved in converting changes in acidity outside of OEC cells into Ca2+ signals within them. Ca2+ signals in response to acidity will be measured in OEC cells using a technique called fluorescent videomicroscopy: this records changes in the brightness of a Ca2+-sensing fluorescent dye placed within OEC cells, using a microscope. The mechanisms involved in these Ca2+ signals will be determined using drugs that inhibit them and by molecular approaches, to decrease their levels. This represents the first step achieving in our long-term goal of developing new types of anti-OEC chemotherapy, targeting mechanisms involved in generating acid-stimulated Ca2+ signals.

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Start date
2020
End date
2021
Principal Investigator
Dr John Mackrill
Researcher
Alana Cutliffe
Institution
UCC
Grant Funding
BCR Project Grant
Cancer Type
Oesophageal
Linked to Breakthrough Cancer Research Priorities
1,

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