SATB1 Expression Is Associated with Biologic Behavior in Colorectal Carcinoma In Vitro and In Vivo

Jie Zhang,Michael A Mcnutt,Donghong Zhang,Yuqing Liu,Xumei Zhang,Baogang Zhang,Shijun Lu,Xiaolong Wei,Mingyu Wang,Yingui Sun,Zhijuan Lin,Na Niu,Ramon Andrade De Mello

doi:10.1371/journal.pone.0047902

Abstract

There is increasing evidence that Special AT-rich sequence-binding protein 1 (SATB1) is aberrantly expressed in several cancers and is correlated with clinicopathologic parameters in these tumors. In this study, we showed over-expression of SATB1 in 80 cases of colorectal cancer and in 3 colorectal cancer cell lines and found expression levels were strongly associated with tumor differentiation and stage. Expression levels of SATB1 protein were higher in poorly-differentiated as compared with well-differentiated cell lines, and both quantity and distribution patterns of SATB1 were associated with tumor differentiation and pTNM stage. Strikingly, we further investigated the effect of down regulation of SATB1 expression on malignant phenotypic features in colorectal cancer cells in vitro, and showed that SABT1 down-regulation negatively affected growth potential, anchorage-independent colony formation and cancer cell invasion, and resulted in increased apoptosis. SATB1 expression was positively associated with the expression of various biological and genetic markers, including Cyclin D1, MMP-2, NF-κB, and PCNA, and was associated with loss of APC and BRAFV600E. These findings suggest that SATB1 is involved in the carcinogenesis, development and progression of colorectal cancer.

Highlights

Special AT-rich sequence-binding protein 1 (SATB1) which was first identified in T cells is important in chromatin organization, and is involved in the regulation of hundreds of genes [1,2]
We studied the effect of SATB1 on apoptosis in colorectal cancer cells using flow cytometry with the Annexin V-PI kit
As a global chromatin organizer and transcription factor, SATB1 is a key gene in T cell development [27] and erythoid differentiation [5]

Summary

Introduction

Special AT-rich sequence-binding protein 1 (SATB1) which was first identified in T cells is important in chromatin organization, and is involved in the regulation of hundreds of genes [1,2]. Under physiological conditions, it plays major roles in T-cell development, early erythroid differentiation, cellular homeostasis and response to various stimuli [3,4,5,6]. SATB1 regulates the expression of more than 1000 genes which are involved in 61 kinds of biological activity such as proliferation, apoptosis, DNA organization, electron transport, protein generation, receptor activity and so on. Current knowledge of the specific mechanisms of CRC metastasis is limited, the function of SATB1 in progression and metastasis of breast cancer raises the possibility it may function in a similar manner in CRC

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