Who Is Andrea Dorfleutner?

I was born and raised in Vienna, the capital of Austria, where I got my masters degree in Cell Biology, Genetics and Immunology from the University of Vienna in 1999. However, for my PhD thesis I decided to leave my home country and work on a collaborative research project between the University of Vienna and The Scripps Research Institute in La Jolla, California. During this time I was awarded a graduate fellowship from the Austrian Academy of Sciences and at the completion of the project I graduated with honors from the University of Vienna. In 2003 I was offered a postdoctoral position at the Mary Babb Randolph Cancer Center in Morgantown, WV, where I started to work on a protein that is associated with the actin cytoskeleton of cells. I discovered that this protein, called AFAP1 is highly expressed in breast cancer cells that have the capability to move around and metastasize. However, in normal breast epithelial cells or breast cancer cells that do not metastasize this protein is barely detectable. I found this very fascinating and ever since I am trying to answer the question on if and how a single protein could make such a huge difference. In addition I am intrigued to figure out if a treatment targeting this protein could some day prevent breast cancer metastasis, which is the main cause of mortality in breast cancer. In 2007 I moved to Chicago and was offered a research assistant professor position at the Feinberg School of Medicine at Northwestern University, which is giving me the opportunity to establish my own research lab. This is very exciting and I am facing new challenges every day. I am now studying how AFAP1 is able to facilitate cell movement and metastasis and aim to identify a strategy to interrupt this process, which might lead to the development of novel breast cancer treatment strategies that prevent breast cancer cell metastasis and therefore better survival for women that are diagnosed with breast cancer.

Why is Andrea Dorfleutner’s research important?

Breast cancer is the most common and fatal type of cancer among women in the US. It develops when normal cells within the breast tissue change and develop malignant properties, such as uncontrolled growth, invasion and destruction of adjacent tissues, and spread to other locations in the body, called metastasis. While non-metastasizing breast cancer is not life-threatening, patients with metastasizing breast cancer have a five-year survival rate of only 20%. In addition, patients with non-metastasizing breast cancer are at risk of developing metastasizing breast cancer. Only 1-5% of women have metastatic disease at the time of breast cancer diagnosis. Therefore an early treatment that blocks metastasis would dramatically change the outcome or most patients and increase their chance for remission. Metastases account for the majority of patient’s deaths due to cancer, and yet current treatments are mainly focusing on preventing primary tumor growth. Thus understanding the metastatic process is of utmost importance and is highly significant for the development of novel treatments.

In order to metastasize, tumor cells have to move away from the primary tumor and invade surrounding tissues. They traffic to distant sites, interact with extracellular matrix and organ tissues and form a secondary tumor. These processes are highly dynamic and require adjustments of the cell shape as well as the adhesive and motile properties of tumor cells, which are controlled by the actin cytoskeleton. Dynamic actin cytoskeletal changes involve the recruitment and modification of actin binding proteins. Therefore we aim to contribute to a better understanding of the molecular mechanisms involved in dynamic actin remodeling in metastasizing breast cancer cells in order to identify novel strategies for breast cancer treatments that prevent cancer cell metastasis.

We recently identified that high expression of the actin binding and crosslinking protein AFAP1 correlates with the ability of breast and prostate cancer cells to invade and metastasize. In the absence of AFAP1, breast cancer cells show a reduced capacity to attach to a substrate, indicating that AFAP1 expression is required for the attachment phase of metastasis. In addition, AFAP1 is phosphorylated upon breast cancer cell adhesion, and we hypothesize that this protein modification changes it’s actin binding and crosslinking properties in order to allow the dynamic actin remodeling required for metastasis. Therefore we propose to investigate 1) the mechanism of AFAP1 phosphorylation and 2) the functional consequences of AFAP1 phosphorylation on cellular processes of breast cancer metastasis: cell attachment, migration and invasion. Delineating the function of AFAP1 in breast cancer cell metastasis might enable the development of novel therapies in the future, which disrupt the function of AFAP1 and subsequently prevent breast cancer metastasis, thus resulting in a higher survival rate of breast cancer patients.