Two articles by IDIBAPS/ICREA involve ZEB1 in tumor invasiveness and muscle differentiation

ZEB proteins (ZEB1 and ZEB2) have recently gained great relevance in molecular oncology because their role promoting invasiveness and metastasis in a number of human cancers through the induction of stemness markers and repression of epithelial adhesion genes. Two articles published this month by the Group of Transcriptional Regulation of Gene Expression, an IDIBAPS team led by an ICREA professor, have found new roles for ZEB1 in tumor invasiveness and muscle differentiation

ZEB1 in the remodeling of the stroma during tumor invasiveness and metastasis

A new study by the Group of Transcriptional Regulation of Gene Expression at IDIBAPS has found that ZEB1 promotes tumor invasion by controlling genes involved in the proteolytic remodeling of the peritumoral stroma. The first authors of the study are E. Sánchez-Tilló and O. de Barrios (equal contribution). ZEB1 regulates in opposite directions the two components of the plasminogen activator system: inducing expression of uPA and inhibiting that of PAI-1. By expanding the mechanisms by which ZEB1 regulates tumor invasiveness, these results reinforce its role as a potential therapeutic target in cancer.

Bibliographic reference: Ester Sanchez-Tillo, Oriol de Barrios, Laura Siles, Pier G Amendola, Douglas S. Darling, Miriam Cuatrecasas, Antoni Castells et al. (January 2013). ZEB1 promotes invasiveness of colorectal carcinoma cells through the opposing regulation of uPA and PAI-1. Clinical Cancer Research. Online First; doi: 10.1158/1078-0432.CCR-12-2675.


ZEB1 inhibits muscle gene expression and differentiation

In addition to its role in cancer progression, ZEB1 also plays crucial roles in embryonic development and cell differentiation. A new article of the Group of Transcriptional Regulation of Gene Expression has found that ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation. The first author of the study is L. Siles. ZEB1 knockdown triggers early protein and mRNA expression of muscle determination and differentiation genes and, accordingly, precocious myotube conversion. Negative regulation by ZEB1 of muscle gene expression and differentiation occurs via its binding to E-boxes in the regulatory regions of target genes and transcriptional repression involving the CtBPcorepressor. Finally, the temporal pattern of muscle differentiation gene expression is accelerated in ZEB1 null (-/-) mouse embryos. Together these results indicate that ZEB1 plays a crucial role regulating the temporal pattern of gene expression during muscle differentiation.

Bibliographic reference: Laura Siles, Ester Sánchez-Tilló, Jong-Won Lim, Douglas S. Darling, Kristen L. Kroll et al. (January 2013). ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation via CtBP-mediated transcriptional repression. Molecular and Cellular Biology. Ahead of print; doi: 10.1128/?MCB.01259-12.