Examination of the Effects of Acid-Exposure on Oesophageal-Cancer Cells: Examining its Effects on Calcium (Ca2+) Signals which Promote Cancer Growth
Oesophageal cancers (OCs) are the sixth-leading cause of cancer-related deaths worldwide. Oesophageal Adenocarcinoma (OAC) is the most common type in Western Europe and its incidence is rising. OAC has poor survival rates, with a lot of patients being resistant to current chemotherapies.
The top-ranking, risk-factor for OAC-development is “Barrett’s Oesophagus” (BO). Here, the cells normally lining the oesophagus change in shape, size and function. Another risk-factor, linked to BO, is gastro-oesophageal reflux disease (GORD). Here, stomach acid and bile acids enter and irritate the oesophagus.
Our project focuses on largely-unexamined molecular targets in OAC: Ca2+-signalling proteins. Ca2+ is a messenger in the cell and regulates several aspects of cell biology. The amount of Ca2+ in a cell is controlled by Ca2+-signalling proteins: a family with over one-thousand members. Some of these proteins sense acid outside the cell and modify Ca2+ within the cell accordingly. In cancer cells, such modification results in tumour growth and spread.
Little to no work has been carried-out on the distribution of Ca2+-signalling proteins in the cell and OAC patient survival. Even less research has been carried-out on how certain Ca2+-signalling proteins may be sensing acidic environments and be remodelled to favour cancer-formation.
Working with OAC and normal oesophageal cells, we will use state-of-the-art, laboratory techniques to investigate whether OAC is driven by Ca2+ signalling and if this signalling is, in turn, stimulated by acid. The characterization of such pathway(s) would help in the development of novel chemotherapeutic drugs.Back