Profile
Project Title: Investigating the effects of E-cadherin dynamics on EGFR, STAT and related signalling pathways.
Summary: Cell-cell adhesion is the process by which neighbouring cells connect and interact. It plays a pivotal role during embryonic development, regulating the formation of distinct tissue layers. In adults, it is essential to maintain tissue architecture and integrity. Alterations in adhesion-associated protein expression are linked with various diseases, including cancer. The loss of cell-cell adhesion is one of the major hallmarks of cancer, highlighting its importance for homeostasis in healthy tissue.
The transmembrane protein E-cadherin mediates epithelial cell-cell adhesion. The levels of E-cadherin at the cell membrane dictate adhesion strength and cell proliferation and rearrangements. E-cadherin surface levels are regulated via endocytosis and its subsequent recycling or degradation. Increasing evidence suggests that E-cadherin interacts and regulates several signalling pathways essential for cell proliferation and survival. These include the epidermal growth factor receptor (EGFR) family. A negative feedback loop between EGFR and E-cadherin has been observed in various cancer cells, resulting in EGFR activation and E-cadherin loss. However, EGFR and E-cadherin co-exist during embryonic development and homeostasis in normal tissues; the mechanisms underlying this relationship are unknown. Furthermore, our lab recently discovered that E-cadherin modulates non-canonical Signal Transducer and Activator of Transcription (STAT) signalling in Drosophila, independently of its canonical receptor, Janus Kinase. This effect of E-cadherin modifies STAT’s role in heterochromatin stabilisation and promotes programmed cell death.
I intend to investigate these E-cadherin interactions using human epithelial cells. Understanding the molecular mechanisms of these relationships during epithelial homeostasis will provide insight into the observed effects of E-cadherin loss in cancer cells and, thus, potential targets to reverse them.
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