Principal Investigator Robert Weinberg
We have been working with a series of 6-7 transcription factors (TFs) that are expressed transiently during embryogenesis when they program the EMT. These TFs are found to be expressed by invasive and metastatic cells, on which they confer many of the cell phenotypes of high-grade malignancy. In fact, these TFs rarely act alone, but instead intercommunicate and form a complex circuitry that enables them to collaborate to induce the EMT. We are attempting to understand the organization of the signaling circuitry that enable the various EMT-inducing TFs to induce this profound cell-biological change in normal and neoplastic cells. In addition, we are studying the downstream consequences of the actions of these TFs in terms of the genes whose expression they induce and the cell-biological consequences of this induction. We anticipate that gene expression array analyses will allow us to define a core EMT gene expression program that should prove important in understanding the biochemical mechanisms of cancer cell invasion and metastasis and, at the same time, provide indications of useful diagnostic markers to indicate the presence of cells that possess malignant potential within tumors.