Seminar/ Colloquium

Title : Signaling to chromatin: Tale of SATB family genome organizers
Speaker: Sanjeev Galande, Indian Institute of Science Education and Research (IISER)
Date : 16/09/2016, Seminar Hall, First Floor.

Abstract:

The chromatin organizer SATB1 has been implicated in the development and progression of multiple cancers including breast and colorectal cancers. However, the regulation and role of SATB1 in colorectal cancers is poorly understood. Here, we demonstrate that expression of SATB1 is induced upon hyperactivation of Wnt/β-catenin signalling and repressed upon depletion of TCF7L2 (TCF4) and β-catenin. We show that direct binding of TCF7L2/β-catenin complex on Satb1 promoter is required for regulation of SATB1. Moreover, SATB1 is sufficient to regulate the expression of β-catenin, members of TCF family, multiple downstream effectors and mediators of Wnt pathway. SATB1 potentiates the cellular changes and expression of key cancer-associated genes in nonaggressive colorectal cells, promotes their aggressive phenotype and tumorigenesis in vivo. Conversely, depletion of SATB1 from aggressive cells reprograms the expression of cancer-associated genes, reverses their cancer phenotype and reduces the potential of these cells to develop tumours in vivo. We also show that SATB1 and β-catenin bind to the promoters of TCF7L2 and the downstream targets of Wnt signalling and regulate their expression. Our findings suggest that SATB1 shares feedback regulatory network with TCF7L2/β-catenin signalling and is required for Wnt signalling-dependent regulation of β-catenin. Collectively, these results provide unequivocal evidence to establish that SATB1 reprograms the expression of tumour growth- and metastasis-associated genes to promote tumorigenesis and functionally overlaps with Wnt signalling critical for colorectal cancer tumorigenesis.