Kathryn D. Curtin

PhD, Harvard University, 1995

email: kcurtin@uark.edu

phone: 479-575-4176 (office) or 4886 (lab)

 

Using Drosophila to Study Metastasis

Isolated tumors rarely kill their host; metastasis kills. Indeed, tumor spreading is the essential characteristic of cancer. Though much is known about how primary tumors form, much less is known about the mechanism of metastasis. This is largely due to the absence of a good, easy to manipulate, model system. We are using fruit flies to study metastasis with an emphasis on understanding the function of the metastatic protein basigin in cancer and in normal cells.

Basigin is found on the surface of a variety of metastatic tumors in humans where expression levels correlate with cancer invasiveness. In addition, expression of basigin in mouse tumors leads to increased tumor size and increased tumor invasion. Basigin is also widely expressed in normal tissues. Despite its importance in both cancerous and normal cells, basigin is not a well-studied molecule.

I have found that basigin is required for both normal cell structure and cell-cell interactions. Expression of basigin in insect cells leads to dramatic rearrangement of the cytoskeleton. Removal of basigin in cells in the animal causes a disruption of over-all cell structure, including misplacement of internal organelles. I have also found that basigin interacts with integrins to affect cell structure. Integrins are cell surface proteins that directly link the actin cytoskeleton to proteins outside the cell, especially to proteins in the extracellular matrix (ECM). This link allows cells to attach to and migrate along the ECM by providing an anchor against which cells can exert force to generate motion. Anchoring to the ECM, or to other cells, is also required for cells to maintain a normal internal structure, including normal placement of organelles and basigin and integrin may help provide such a function.

Basigin also affects neuron-glia interactions and this function may not involve integrin. Indeed, several pieces of data suggest that basigin is multi-functional and that it may use different molecular pathways to accomplish distinct cellular functions.

The long term goals of my lab are three fold. First, we are interested in understanding basigin at a molecular level. This includes understanding basigin's physical interactions with integrin as well as identifying other proteins with which basigin interacts. Second, we are interested in correlating information about basigin's molecular interactions with its cellular functions. Third, we are using fruit flies as a model system to understand basigin's role in cancer. Fruit flies provide three important advantages for cancer studies. First, we can generate stationary tumors in a defined tissue so that the site of primary tumor formation is known. Second, we can mark these tumors with green fluorescent protein so that tumors can be readily visualized by simple fluorescent microscopy. Third, we can specifically change the genetic composition of the tumors in defined ways, including altering expression of basigin in tumors, to study the effects on metastasis. This approach makes it possible to identify the exact genetic combinations that lead to cancer.

Students interested in any of these projects are welcome to call, write or visit to talk about this work.

Selected References:

2002 Curtin, K.D., Zhang, Z., and Wyman, R. J. Gap junction genes expressed during development are required for adult neural function in the Drosophila Optic Lamina. J. Neurosci. 22, 7088-7096.

2002 Curtin, K.D., Zhang, Z., and Wyman, R.J.. Gap junction proteins are not interchangeable in development of neural function in the Drosophila visual system. J. Cell Sci. 115, 3379-3388.

2004 Curtin, K.D., Meinertzhagen, I.A., and Wyman, R.J. Basigin (EMMPRIN) interacts with integrin to affect cellular architecture, submitted J. Cell Sci.