Genome organizing function of SATB1 in tumor progression

Abstract

When cells change functions or activities (such as during differentiation, response to extracellular stimuli, or migration), gene expression undergoes large-scale reprogramming, in cell type- and function-specific manners. Large changes in gene regulation require changes in chromatin architecture, which involve recruitment of chromatin remodeling enzymes and epigenomic modification enzymes to specific genomic loci. Transcription factors must also be accurately assembled at these loci. SATB1 is a genome organizer protein that facilitates these processes, providing a nuclear architectural platform that anchors hundreds of genes, through its interaction with specific genomic sequences; this activity allows expression of all these genes to be regulated in parallel, and enables cells to thereby alter their function. We review and describe future perspectives on SATB1 function in higher-order chromatin structure and gene regulation, and its role in metastasis of breast cancer and other tumor types.

SATB1 expression is correlated with β-catenin associated epithelial–mesenchymal transition in colorectal cancer

“…4,22 SATB1 was first reported in 1992 in thymocytes, 23 and it was shown to be involved in the proliferation, development, and differentiation of T cells. 5 More recently, SATB1 has attracted considerable attention due to its role in the promotion of tumor growth and metastasis.…”

High expression of special AT‑rich sequence binding protein‑1 predicts esophageal squamous cell carcinoma relapse and poor prognosis

“…SATB1 can regulate gene expression by folding chromatin into loop domains and tethering DNA domains to the SATB1 network structure (7,8). Under normal conditions, SATB1 is expressed at low levels in cells and tissues, but is overexpressed in a variety of malignant tumors, including laryngeal squamous cell carcinoma, endometrial cancer, hepatocellular carcinoma, rectal cancer, cutaneous malignant melanoma, gastric cancer, prostate cancer, lung cancer and cutaneous T-cell lymphoma (7,(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The expression of SATB1 has been examined in esophageal adenocarcinoma and is an independent prognostic factor (20).…”

“…SATB1 can regulate the expression of >1,000 genes involved in the processes of DNA organization, proliferation and apoptosis (8,9). SATB1 has been demonstrated to serve roles in malignancies, in addition to malignant transformation (7,20).…”

“…The expression of SATB1 has been examined in esophageal adenocarcinoma and is an independent prognostic factor (20). In several types of cancer, including laryngeal squamous cell carcinoma, endometrial cancer, hepatocellular cancer and lung cancer, high expression of SATB1 promotes tumor growth and metastasis, and is a negative prognostic factor (7,(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). SATB1 can regulate the expression of >1,000 genes involved in the processes of DNA organization, proliferation and apoptosis (8,9).…”

Nuclear matrix revisited?

“…While mutations in nuclear lamina proteins have been shown to underlie diseases such as laminopathies, 2 which include symptoms of progeria, subtypes of muscular dystrophy, and neuropathy the function of internal structures in development and disease is less well understood with the notable exception of special ATrich binding protein (SATB1) and its role as a global regulator of gene expression in cancer. 3 Matrin-3 protein is a structural component of internal nuclear network also called "nuclear matrix." The importance of the nuclear matrix in functional organization of chromatin into higherorder loops and "matrix attached" elements has been proposed in 1970s but has been highly debated ever since.…”