Uncontrolled Growth of Cancer
Cancer is the uncontrolled growth of a person’s own cells that have become deformed in some way. Cells can become deformed, or cancerous through mutations, genetic predispositions, or environmental factors, among other things. Cancer is difficult to treat since it is a person’s own cells which are no longer healthy, so treatments that set out to kill cancer cells can have negative effects on healthy cells. You may have seen this with patients who have taken chemotherapy – their hair falls out and they are often sick to their stomachs.
Stages of Cancer
For my project in the Pollock lab, we are focused on late stage breast cancer. The late stage cases, or metastatic cases, are when the cancer has spread to parts of the body other than the breast tissue. Treatment for metastatic breast cancers are more ineffective compared to cancers at any earlier stage. Specifically, we are concerned with reasons why the cancerous cells move from the breast tissue to other parts of the body.
Protein-protein interactions are an important area of study because they facilitate dynamic processes. We are focused on two proteins: 1) ErbB2, commonly known as HER2, and 2) MEMO1. HER2 plays a role in cell motility when it is activated in a cell. In normal, healthy cells, HER2 can become activated with a signal, but then it can also be deactivated when it has finished its task. MEMO1 has the ability to bind to HER2 when it is activated and prevents it from becoming deactivated. The ultimate goal of our project is to find a drug-like molecule that can bind to MEMO1 so the normal function of HER2 can be restored.
Testing the Function of MEMO1
For our studies, we need something that can detect the difference between whether MEMO1 is attached to HER2 or MEMO1 is free from HER2. To do this, we use an experiment called a fluorescence polarization assay. Picture a 6-year old child and his father playing flashlight tag in the middle of the night. Both of them have their flashlights on and are spinning in a circle while you watch from the porch. The child will be able to spin in a circle much faster than his father because of his smaller size. So, you will see the light flash across the night differently from the child versus his father. This is the exact same way we can detect the difference between bound and unbound MEMO1. A fluorescent tag, the flashlight, will either be attached to a small object, a peptide, or a large object, MEMO1.
Testing for a Drug Therapy
To be able to stop the uncontrolled cellar growth associated with cancer, we need to see experimental results that look like the 6-year old child spinning in a circle with his flashlight instead of his father. When we add a drug into the experiment and it binds to MEMO1, we will see results similar to the child spinning with his flashlight. This is how we will be able to tell if we have an effective drug that has a possibility to work against uncontrolled cancer growth.
The protein-protein interaction between HER2 and MEMO1 proves to be an important one for the study of aggressive breast cancers. As we identify drugs that can influence this interaction, we can learn more about the uncontrollable growth of cancer. We hope that our work might lead to answers for how to combat that uncontrollable growth, especially for those cancers that do not currently have effective treatments.
-Courtney Labrecque BMB Class of 2019