SATB1 (special AT-rich binding protein 1) is a global chromatin organizer 
regulating the expression of a large number of genes. Overexpression has been 
found in various solid tumors and positively correlated with prognostic and 
clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression 
and its correlation with poor differentiation, invasive depth, TNM (tumor, 
nodes, metastases) stage and prognosis have been demonstrated. However, more 
detailed studies on the SATB1 functions in CRC are warranted. In this article, 
we comprehensively analyze the cellular and molecular role of SATB1 in CRC cell 
lines with different SATB1 expression levels by using RNAi-mediated knockdown. 
Using siRNAs with different knockdown efficacies, we demonstrate 
antiproliferative, cell cycle-inhibitory and proapoptotic effects of SATB1 
knockdown in a SATB1 gene dose-dependent manner. Tumor growth inhibition is 
confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable 
knockdown cells. The in-depth analysis of cellular effects reveals increased 
activities of caspases-3, -7, -8, -9 and other mediators of apoptotic pathways. 
Similarly, the analysis of E- and N-cadherin, slug, twist, β-catenin and MMP7 
indicates SATB1 effects on epithelial-mesenchymal transition (EMT) and matrix 
breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases 
and (proto-)oncogenes such as HER receptors and Pim-1. Taken together, this 
suggests a more complex molecular interplay between tumor-promoting and possible 
inhibitory effects in CRC by affecting multiple pathways and molecules involved 
in proliferation, cell cycle, EMT, invasion and cell survival.