Control of epidermal growth factor receptor signaling by clathrin signalosomes

Tumours are made up of cells that can be recognized by doctors and scientists by several changes they exhibit compared to normal cells. Some of these changes involve alteration in the abundance and function of proteins found on the outer surface of the tumour cells. These changes in the function of cell surface proteins are required for tumours to grow and spread throughout in the body (metastasis). Hence, obtaining a better understanding of how cells control the function of proteins found on their outer surface has the potential to provide new ways to treat cancer. One of the types of cell surface proteins altered in cancer cells is hormone receptors, in particular one named Epidermal Growth Factor Receptor (EGFR). EGFR signals to cells to grow and migrate and when uncontrolled, these traits can lead to cancer and metastasis. The cell surface is like that of a soccer-ball in that it is made up of "patches". As the hexagonal patches on a soccer ball are of different colours, the "patches" on the outer surface of a cell, termed microdomains, also have unique properties. We have discovered that a particular type of microdomain on the cell surface, called a clathrin signalosome, determines how a cell responds to certain hormones. The hormone receptor EGFR is found within the clathrin signalosomes on the surface of a cell, yet how clathrin signalosomes control hormone receptors such as EGFR remains a mystery. To uncover how clathrin signalosomes control the function of EGFR and thus cancer progression, we will use several different approaches including advanced microscopy of cells engineered to contain fluorescent versions of specific key proteins, allowing us to "see" EGFR within microdomains. This research will reveal how clathrin signalosomes work within healthy and cancerous cells to control EGFR function. Since alterations in the normal function of EGFR cause cancer cells to grow and metastasize, this work may reveal new ways to treat various types of cancer