Chemotaxis is an important and fascinating phenomenon in which signal transduction and cell shape change interact. It is relevant to processes occurring during development, immune responses and to the spread of tumor cells during metastasis. A major focus of the lab is on analyzing breast cancer cell invasion and metastasis. We have found that the EGFR receptor (ErbB1) and its family members ErbB2 and ErbB3 can enhance metastasis without affecting tumor growth rate, and are exploring the implications of these results in more detail. A second theme being pursued is the development of methods for screening genes for effects on intravasation and metastasis in order to speed up the rate of identification of new proteins important for metastasis. We are also interested in applying the methods and models developed studying breast cancer to other tumor types, including glioma and head and neck cancer. The long term goal of these projects is to identify proteins important for cell motility, chemotaxis and metastasis that can be used as targets for drug development and prognosis. A combination of molecular and imaging approaches using mouse models is used to determine the functional significance of specific proteins and signaling pathways.
The lab has also studied Dictyosteliumdiscoideum and Saccharomycescerevisiae. Dictyostelium and Saccharomyces provide a molecular/genetic dissection of chemotaxis. Both utilize G protein-coupled signal transduction pathways to mediate orientation responses. The movies sections demonstrate examples of these valuable model systems for studies of chemotaxis and directed cell responses.
Kedrin D, Wyckoff JB, Hynes NE, Arteaga CL, Segall JE (in press) ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation. Clin. Cancer Res.
Hernandez L, Smirnova T, Kedrin D, Wyckoff J, Stanley ER, Cox D, Muller WJ, Pollard JW, van Rooijen N, Segall JE (in press) EGF/CSF-1 Induced Breast Cancer Cell Invasion is Triggered by Heregulin Beta 1 and CXCL12. Cancer Res.
Hernandez L, Smirnova T, Wyckoff J, Condeelis J, Segall JE (in press) In vivo assay for tumor cell invasion. Methods in Molecular Biology.
Kedrin D, Gligorijevic B, Wyckoff J, Verkhusha VV, Condeelis J, Segall JE, van Rheenen J (2008) Intravital imaging of metastasis through an orthotopic Mammary Imaging Window. Nature Methods. Nature Methods. 5:1019-21
Kedrin D, van Rheenen J, Hernandez L, Condeelis J, Segall JE (2007) Cell motility and cytoskeletal regulation in invasion and metastasis. J. Mam. Gland Biol. Neoplasia. 12:143-52.
Kedrin D, Wyckoff J, Sahai E, Condeelis J, Segall JE (2007) Imaging of tumor cell movement in vivo. Current Protocols in Cell Biology. 19.7.1 – 19.7.17.
Pu J, McCaig CD, Cao L, Zhao Z, Segall JE, Zhao M. (2007) EGF receptor signalling is essential for electric-field-directed migration of breast cancer cells. J Cell Sci. 120 :3395-403.
Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J. (2007) Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 67:2649-56.
Wang W, Wyckoff JB, Goswami S, Wang Y, Sidani M, Segall JE, Condeelis JS. (2007) Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors. Cancer Res. 67:3505-11.
Xue C, Wyckoff J, Liang F,Sidani M, Violini S, Tsai K-L, Zhang Z-Y, Sahai E, Condeelis J, Segall JE (2006) EGF receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis. Cancer Res. 66:192-7
Xue C, Liang F, Mahmood R, Vuolo M, Wyckoff J, Qian H, TsaiK-L, Kim M, Locker J, Zhang Z-Y, Segall JE (2006) ErbB3-dependent motility and intravasation in breast cancer metastasis. Cancer Res. 66: 1418-1426.
Chen C, Segall JE (2006) EppA, a putative substrate of DdERK2, regulates cyclic AMP relay and chemotaxis in Dictyosteliumdiscoideum. Eukaryot Cell. 5:1136-46.
Kempiak SJ, Yamaguchi H, Sarmiento C, Sidani M, Ghosh M, Eddy RJ, Desmarais V, Way M, Condeelis JS, Segall JE (2005) J. Biol. Chem. 280:5836-5842.
Goswami S, Sahai E, Wyckoff J, Cox D, Pixley F, Stanley ER, Segall JE, Condeelis, J (2005) Macrophages promote the invasion of carcinoma cells in vitro via a paracrine loop. Cancer Res. 65:5278-83.
Condeelis J, Singer R, Segall JE (2005) The great escape: When cancer cells hijack the genes for chemotaxis and motility. Ann. Rev. Cell Dev. Biol. 21: 695-718.