Acid-stimulated Ca2+ signals as a potential therapeutic target for the treatment of oesophageal cancer

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 cells 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 video microscopy: which 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.

Alana L. Cutliffe and Dr John J. Mackrill

Research Findings


Cutliffe AL, McKenna SL, Chandrashekar DS, Ng A, Devonshire G, Fitzgerald RC, O’Donovan TR, Mackrill JJ. Alterations in the Ca2+ toolkit in oesophageal adenocarcinoma. Explor Target Antitumor Ther. 2021;2(6):543-575. doi: 10.37349/etat.2021.00063. Epub 2021 Dec 31. PMID: 36046118; PMCID: PMC9400700.
Start Year:
End Year:
Principal Investigator
Dr John Mackrill
Alana Cutliffe
Grant Funding
Breakthrough Project Grant
Cancer Type
Linked to Breakthrough Cancer Research Priorities
1, 3, 4, 5

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