Frank Gertler
Scientist
Ludwig Center at MIT
Massachusetts Institute of Technology
United States of America
Biography
My laboratory studies how contextual signals are integrated by intracellular signaling pathways to orchestrate directed cell movement and thus tumor cell invasion. One important research area focuses on Mena, a molecule that regulates actin polymerization and cell:matrix/cell:cell adhesion. Changes in alternative splicing of the Mena mRNA during the epithelial-to-mesenchymal transition and during tumor progression produce distinct Mena protein isoforms with significantly different functions. In primary carcinomas, an epithelial-specific Mena isoform enhances cell:cell adhesion and suppresses invasion and metastasis. However, as tumors progress to malignancy another change alternative splicing produces an invasion-specific Mena isoform that promotes cell motility and chemotaxis, exerting a potent pro-metastatic effect on carcinoma cells. Fascinated by the divergent functions conferred to Mena by alternative splicing, we also are investigating the role of alternative splicing in metastatic progression.
Research Interest
Intracellular signaling pathways, tumor cell invasion, cell movement
Publications
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Mejillano MR, Kojima S, Applewhite DA, Gertler FB, Svitkina TM, Borisy GG. Lamellipodial versus filopodial mode of the actin nanomachinery: pivotal role of the filament barbed end. Cell. 118:363-73 (2004).
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Shapiro, I.M., Cheng, A.W., Flytzanis, N.C., Balsamo, M., Condeelis, J.S., Oktay, M.H., Burge, C.B., and Gertler, F.B. (2011). An EMT-Driven Alternative Splicing Program Occurs in Human Breast Cancer and Modulates Cellular Phenotype. PLoS Genet. 7, e1002218.
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Gupton, S.L., Riquelme, D., Hughes-Alford, S.K., Tadros, J., Rudina, S.S., O Hynes, R., Lauffenburger, D., and Gertler, F.B. (2012). Mena binds α5 integrin directly and modulates α5β1 function. The Journal of Cell Biology 198, 657–676.
