SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer.

Special AT-rich sequence-binding protein 1 and 2 (SATB1/2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB2 acts as a tumor suppressor in laryngeal squamous cell carcinoma and colon cancer, whereas SATB1 promotes the progression of numerous types of cancers. In this study, we examined the effects of SATB1 and SATB2 on the malignant characteristics of colorectal cancer cells. SATB1 and SATB2 expression were negatively correlated in colorectal cancer specimens. SATB1 expression was increased, whereas SATB2 expression was reduced, in colorectal cancer tissues compared to control tissues. Exogenous expression of SATB2 in colorectal cancer cells suppressed cell proliferation, colony formation and tumor proliferation in mice. c-Myc was reduced by SATB2 expression, and exogenous expression of c-Myc in SATB2-expressing cells restored proliferation, colony formation and in vivo tumor growth of colorectal cancer cells. We also showed that c-Myc reduction by SATB2 was mediated by the inactivation of ERK5. In contrast, SATB1 promoted c-Myc expression. The expression of SATB1 in colorectal cancer tissues was positively correlated with c-Myc expression, and SATB1 knockdown reduced c-Myc expression in colorectal cancer cells. Finally, we showed that SATB1 knockdown in colorectal cancer cells suppressed cell proliferation, colony formation and cell invasion. Our results reveal interesting features of how the structural homologs SATB1 and SATB2 exert opposing functions in colorectal tumorigenesis.