Aristidis Moustakas research group

TGF-β SIGNALING AND CANCER CELL DIFFERENTIATION

Our research program covers several aspects of signal transduction and basic cancer biology. We have a particular emphasis on the developmental process of epithelial-mesenchymal transition (EMT) and its links to tumor metastasis and cancer stem cell biology. EMT confers upon cancer cells capacities that are required for metastasis. We want to explain how the EMT process contributes to the maintenance of cells that carry tumor-initiating and metastasis-initiating capacities. Our efforts to develop novel chemicals that inhibit the EMT promise to take our research to more applied areas of medical science.

From the signal transduction perspective, the lab focuses on the Transforming Growth Factor β (TGFβ) pathway and on nuclear events such as regulation of transcription. We also study cytoplasmic signaling events, particularly the mechanisms of cell polarity regulation by the tumor suppressor kinase LKB1 and its downstream effectors, the AMP-regulated kinase (AMPK) family.

TGFβ regulates cellular processes such as cell growth, differentiation and tumorigenesis via a group of proteins known as Smads and via several intracellular kinase and GTPase pathways. The Smads transmit signals from type I and type II TGFβ receptors on the cell surface into the cell nucleus, where they regulate gene expression. TGFβ signaling has a complex impact on tumorigenesis. The pathway suppresses the growth of early stage tumors by inhibiting cell growth or by prompting cells to undergo apoptosis, but nevertheless, drives tumorigenesis in late-stage tumors. We investigate the function and regulation of various TGFβ-responsive genes by combining functional experiments with global gene expression analysis in several models of epithelial cells. This approach has allowed us to decipher key steps in the genetic program that mediates tumor suppression or tumor progression in response to TGFβ.