Professor

PhD: University of California, Berkeley
Postdoctoral Training: Center for Cancer Research, MIT

Joined the faculty: 2004

Affiliations: MBR Cancer Center

Teaching: BMS 705, CCB 700, CCMD 793L, CCMD 793M, CCMD 730

Office: 2836 HSS
Phone: (304) 293-2980
Fax: (304) 293-4667
Email: sfrisch@hsc.wvu.edu

Anoikis. Our laboratory discovered the phenomenon of "anoikis” -- apoptosis that is triggered by detachment of cells from their matrix or attachment to an inappropriate matrix. Anoikis safeguards against the circulation and colonization of cells released from normal epithelial tissues or from tumors. It is therefore critical for preventing metastasis. Anoikis conceptually bridges the cell adhesion/signal transduction/cytoskeleton and the apoptosis fields; its fundamental mechanisms remain to be discovered. The mechanism of anoikis and the development of novel cancer therapeutics based on this mechanism is a major focus of the laboratory.

Caspase-8 as a cell migration/tumor invasion gene.

Caspase-8 is widely known for its proapoptotic role, but our findings reveal that it is also a cell migration, cell adhesion and tumor cell invasion factor. It appears to function partly by activating the calpain family of proteases and partly by binding to and activating the p85 subunit of PI3-kinase, leading to increased activation of Rac and ensuing migration. These mechanisms are being investigated in more detail and a mouse model to test the hypothesis that caspase-8 is a pro-metastatic gene is being constructed presently.

  References:

• Frisch, S.M. Caspase-8: Fly or Die. Cancer Res. 68: 4491-4493, 2008.
   
• Senft, J., Helfer, B. and Frisch, S.M. Caspase-8 interacts with the p85 subunit of phosphatidylinositol-3-kinase to regulate cell motility, adhesion and Rac activation. Cancer Res. 67: 11505-11509, 2007.
   
• Huang, X.D., Masselli, A., Frisch, S.M., Hunton, I., Jiang, Y., Wang, J.Y.J. Blockade of TNF-induced Bid cleavage by caspase-resistant Rb. J. Biol. Chem. 282: 29401-13, 2007.
   
• Helfer, B., Boswell, B.C., Finlay, D., Cipres, A., Vuori, K., Kang, T.B., Wallach, D., Dorfleutner, A., Lahti, J.M., Flynn, D.C. and Frisch, S.M. Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions. Cancer Res. 66: 4274-4278, 2006.
   
• Bian, D. , Mahanivong, C., Yu, J., Frisch, S.M., Pan, Z., Ye, R. and Huang, S. The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration. Oncogene 25: 2234-2244, 2005.
   
• Screaton RA, Kiessling S, Sansom OJ, Millar CB, Maddison K, Bird A, Clarke AR, and Frisch SM. Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: a potential link between genome surveillance and apoptosis. Proc. Natl. Acad. Sci. 100: 5211-5216, 2003.