Research Groups
Research Groups > Charles Streuli
Recent key publications
Wang P, Ballestrem C, Streuli CH. (2011). The C’-terminus of talin links integrins to cell cycle progression. J. Cell Biol.195, 499-513. PubMed
Du J-Y, Chen M-C, Hsu T-C, Wang J-H, Brackenbury L, Lin T-H, Yang Y, Streuli CH, Lee Y-J. (2011). The RhoA-Rok-myosin II pathway is involved in extracellular matrix mediated regulation of prolactin signaling in mammary epithelial cells. Journal of Cellular Physiology. doi: 10.1002/jcp.22886. PubMed
Akhtar, N., Marlow, R., Lambert, E., Schatzmann, F., Lowe, E. T., Cheung, J., Katz, E., Li, W., Wu, C., Dedhar, S., Naylor, M. J., and Streuli, C. H.(2009) Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation, Development136, 1019-27 PubMed
CHARLES STREULI MA PhD
Integrins in breast biology
The research in our laboratory is focussed on how cell-matrix interactions control the development and function of epithelial cells. We study the mammary gland becasue it is an excellent system to uncover basic principles of cell and developmental biology. Understanding how normal mammary epithelial cells work is revealing new targets and pathways for treating breast cancer.
Cell-matrix: controlling breast function
All cellular processes are determined by adhesive interactions between cells and their local microenvironment. To be organised properly in tissues, cells bind to each other, and they also interact with the extracellular structural material that forms the bulk of tissues, the extracellular matrix (ECM). Some of the specific receptor molecules that bind cells to the ECM, called integrins, are essential for controlling nearly all aspects of cell behaviour, such as cell survival and growth, their ability to make tissue-specific proteins, and their capacity to move. All of these cellular characteristics are required for tissues to form and function properly, and they are some of the most recognizable features to be altered in cancer cells.
Our laboratory is interested in how cell-ECM interactions control the development and function of the mammary gland. This tissue contains ducts, which develop in puberty, and alveoli, which are made just during pregnancy and lactation. The alveoli are milk factories and the ducts are tubes that transport milk to the nipples. Sometimes, cells of either ducts or alveoli can become cancerous. It turns out that one of the central problems in cancer is that cell adhesion becomes altered. Either the integrin receptors change subtly, or the enzymes that they control become altered or mutated, so that the cells don’t know how to behave properly.
We are discovering the specific details for how the integrin ECM receptors are involved with the development of ducts; how they control cell growth in the mammary gland; how mammary cells make milk; and how they know which way up they are. We hope that by understanding the behaviour of normal breast epithelial cells, we will bring to light new possibilities for treating breast cancer.
The scientific story
A long standing interest of our research group is to find out how the integrin class of adhesion receptors controls the way that epithelial cells work. It is now well established that the cellular microenvironment controls the way that tissues develop, and that alterations in the interactions between cells and their ECM cause diseases such as cancer. To understand these processes in detail, we are focussing on the intracellular mechanisms of how integrins control breast development, function, and tumorigenesis.
Integrins are membrane-bound heterodimeric receptors that bind to ECM proteins on the outside of the cell, and
on the inside of the cell they assemble numerous adapter proteins and enzymes into adhesion complexes. These complexes are situated at ECM attachment sites, and they organise the cytoskeleton and control signalling enzymes. The lab is using genetic approaches to determine the molecular basis for how integrins control cell-fate decisions in breast epithelial cells.
We have developed inducible Cre-Lox approaches for deleting integrin and integrin signalling genes in vivo and in primary cell culture models. In combination with our use of lentiviral-mediated gene silencing with shRNAmirs, we have discovered that β1-integrins specifically control cell cycle, polarity, and tissue-specific gene expression patterns in breast epithelial cells. We are now dissecting the molecular details of how integrins and their signalling enzymes/adaptors such as integrin-linked kinase, focal adhesion kinase and the small GTPase Rac1, control these processes. New approaches include the use of breast stem cells, 4D imaging techniques with genetically marked cells, and models of breast cancer.
Our work is providing new insights into how organs develop and function, and it is revealing some of the underlying abnormalities that occur in breast cancer.