EMT; epigenetics; breast cancer; metastasis; transcription factors
Lotz-Jenne Carina, Lüthi Urs, Ackerknecht Sabine, Lehembre François, Fink Tobias, Stritt Manuel, Wirth Matthias, Pavan Simona, Bill Ruben, Regenass Urs, Christofori Gerhard, Meyer-Schaller Nathalie (2016), A high-content EMT screen identifies multiple receptor tyrosine kinase inhibitors with activity on TGFβ receptor., in Oncotarget
, 7(18), 25983-6002.
Kuzmanov Aleksandar, Hopfer Ulrike, Marti Patricia, Meyer-Schaller Nathalie, Yilmaz Mahmut, Christofori Gerhard (2014), LIM-homeobox gene 2 promotes tumor growth and metastasis by inducing autocrine and paracrine PDGF-B signaling., in Molecular oncology
, 8(2), 401-4016.
Fantozzi A, Gruber DC, Pisarsky L, Heck C, Kunita A, Yilmaz M, Meyer-Schaller N, Cornille K, Hopfer U, Bentires-Alj M, Christofori G (2014), VEGF-mediated angiogenesis links EMT-induced cancer stemness to tumor initiation, in Cancer Research
, 74(5), 1566-1575.
Tiwari Neha, Meyer-Schaller Nathalie, Arnold Phil, Antoniadis Helena, Pachkov Mikhail, van Nimwegen Erik, Christofori Gerhard (2013), Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8)., in PloS one
, 8(2), e57329-e57329.
Tiwari Neha, Tiwari Vijay K, Waldmeier Lorenz, Balwierz Piotr J, Arnold Phil, Pachkov Mikhail, Meyer-Schaller Nathalie, Schübeler Dirk, van Nimwegen Erik, Christofori Gerhard (2013), Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming., in Cancer cell
, 23(6), 768-83.
The formation of metastasis from a primary tumor is achieved through a metamorphosis of adherent tumor cells to highly migratory and invasive cells. We are particularly interested in the fundamental questions on how these cells with an original epithelial imprinting de-differentiate into metastatic tumor cells with a mesenchymal gene expression profile. During this process, also known as EMT (epithelial to mesenchymal transition), tumorigenic cells undergo a major transcriptional reprogramming that leads to the conversion of benign, adhesive cells to malignant, invasive cells. The massive changes in gene expression during EMT argue for a critical role of master regulators that act on the level of chromatin modifications and direct transcriptional control. To study the epigenetic control of cellular de-differentiation, we induce EMT in vitro by the addition of TGFb to murine epithelial cells and follow the transcriptional and phenotypic changes over time. By combining RNAi screening approach together with microarray analysis and chromatin-immunoprecipitation, we aim at deciphering the complex networks driving EMT. More specifically, we will use a phenotypic microscopy-based screen of transcription (co)factors as well as a functional migration screen to identify and hierarchically group the factors regulating EMT. We are especially interested in epigenetic modifiers and their contribution to EMT and tumor metastasis. Using this approach, we hope to gain a more global understanding of the processes underlying malignant tumor progression and metastasis.