Department of Pathology
330 Brookline Avenue
Boston, MA 02215
Lab Members: 7 postdoctoral fellows, 3 graduate students
Visit my lab page here.
A major research focus in the laboratory is the regulation of carcinoma cell migration and invasion, with emphasis on the signaling pathways which impact this phenotype. Work in our laboratory has focused on the role of the PI 3-K and Akt signaling pathway in modulating breast cancer progression. We have discovered that Akt1 is breast cancer cell motility and invasion suppressor, a surprising finding considering that the PI 3-K and Akt pathway is clearly implicated in tumor progression (Yoeli-Lerner, Mol. Cell 2005). More recent studies have uncovered specific substrates of Akt isoforms and the mechanisms by which they modulate breast cancer invasion and metastasis in vivo (Chin, Mol Cell 2010). We are also investigating the relative contribution of additional PI 3-K effectors, including the SGK (serum and glucocorticoid-regulated kinases) family of protein kinases. Similarly, we are investigating the isoform specific functions of PI 3-kinases at modulating cancer progression.
Additional studies are focusing on the transcription factors of the NFAT (Nuclear Factor of Activated T cells) family. We have found that NFATs are expressed and functionally active in cancer cells, and that NFAT transcriptional activity is required for promoting carcinoma invasion (Jauliac, NCB 2002). The significance of these studies is that they afford insight into a gene, NFAT, not previously known as being important for human carcinoma invasion and metastasis, and may thus provide a novel approach for targeted drug design for anti-tumor therapies.
Jauliac, S., López-Rodriguez, C., Shaw, L. M., Brown, L. F., Rao, A. and Toker, A. The Role of NFAT Transcription Factors in Integrin-Mediated Carcinoma Invasion. (2002) Nature Cell Biology, 4: 540-544.
Yoeli-Lerner, M., Yiu, G. K., Erhardt, P., Jauliac, S. and Toker, A. Akt/PKB blocks breast cancer cell motility and invasion through the transcription factor NFAT. (2005) Molecular Cell, 20: 539-550.
Chin, Y. R. and Toker, A. The actin bundling protein Palladin is an Akt1-specific substrate that regulates breast cancer cell migration. Molecular Cell 2010; 38: 333-344.
Mancini, M. L. and Toker, A. NFAT Proteins: Emerging Roles in Cancer Progression. Nature Reviews Cancer 2009; 9: 810-820.
For a complete listing of publications click here.
Last Update: 7/27/2012