BBS Faculty Member - Alex Toker

Alex Toker

Department of Pathology

Beth Israel Deaconess Medical Center
CLS Building, Room 633A
Three Blackfan Circle
Boston, MA 02115
Tel: 617-735-2482
Fax: 617-735-2480
Email: atoker@bidmc.harvard.edu
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.



Last Update: 6/2/2014



Publications

For a complete listing of publications click here.

 


 

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.

Christoforides, C. V., Rainero, E., Brown, K. K., Norman, J. C. and Toker, A. PKD Controls avb3 Integrin Recycling and Tumor Cell Invasive Migration Through its Substrate Rabaptin-5. Developmental Cell 2012; 11;23(3):560-72

Chin YR, Yoshida T, Marusyk A, Beck AH, Polyak K, Toker A. Targeting Akt3 Signaling in Triple Negative Breast Cancer. Cancer Res. 2013; 74(3):964-73

Chin YM, Yuan X, Balk SP, Toker A. PTEN-deficient tumors depend on Akt2 for maintenance and survival. Cancer Discovery. 2014 May 16. doi:10.1158/2159-8290.CD-13-0873



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