The Role of SATB1 in Tumour Progression and Metastasis

Abstract

Carcinogenesis is a long-drawn, multistep process, in which metastatic spread is an unequivocal hallmark of a poor prognosis. The progression and dissemination of epithelial cancers is commonly thought to rely on the epidermal-mesenchymal transition (EMT) process. During EMT, epithelial cells lose their junctions and apical-basal polarity, and they acquire a mesenchymal phenotype with its migratory and invasive capabilities. One of the proteins involved in cancer progression and EMT may be SATB1 (Special AT-Rich Binding Protein 1)—a chromatin organiser and a global transcriptional regulator. SATB1 organizes chromatin into spatial loops, providing a “docking site” necessary for the binding of further transcription factors and chromatin modifying enzymes. SATB1 has the ability to regulate whole sets of genes, even those located on distant chromosomes. SATB1 was found to be overexpressed in numerous malignancies, including lymphomas, breast, colorectal, prostate, liver, bladder and ovarian cancers. In the solid tumours, an elevated SATB1 level was observed to be associated with an aggressive phenotype, presence of lymph node, distant metastases, and a poor prognosis. In this review, we briefly describe the prognostic significance of SATB1 expression in most common human cancers, and analyse its impact on EMT and metastasis.

SATB1 Knockdown Inhibits Proliferation and Invasion and Decreases Chemoradiation Resistance in Nasopharyngeal Carcinoma Cells by Reversing EMT and Suppressing MMP-9

“…The special AT-rich sequence binding protein 1 (SATB1), a transcription factor and a global genome organizer, is involved in pathogenesis and progression of numerous human cancers 7 , 8 . Aberrant expression of SATB1 has been found to be associated with proliferation, invasion, metastasis and poor prognosis in various cancers 8 , 9 . SATB1 was also identified as an independent prognostic marker in many types of cancer 8 , 10 .…”

SATB1 protein is associated with the epithelial‑mesenchymal transition process in non‑small cell lung cancers

“…Although the complex network of molecular factors orchestrating EMT has been extensively studied over the past 20 years, there are still unanswered questions and challenging topics to be explored. In recent years, there has been a growing interest in special AT-rich binding protein 1 (SATB1), a potent transcriptional regulator whose role in EMT was confirmed, among others, in breast, colorectal, prostate and bladder cancers ( 65 ). In these neoplasms, SATB1 was demonstrated not only to be associated with a high tumour malignancy and a poor patient prognosis, but also to promote an invasive, mesenchymal phenotype of the cells ( 65 ).…”

Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy

“…A continuous increased expression of SATB1 has been described to convert inflammatory anti-tumor DCs into pro-tumor DCs by enhanced secretion of pro-tumorigenic cytokine IL-6 and immunosuppressive factor Galectin-1, activating immune-evasive pathways in these cells [ 7 ]. Accordingly, SATB1 has been found to be overexpressed in a wide range of tumors, including breast, lung, pancreas, colorectal, liver, bladder, prostate and ovarian cancer, and has been associated with tumor progression and poor prognosis [ 19 ]. Additionally, next to its role in the direct activation of IL-6 transcription, Kruppel-like factor 4 (KLF4) modulates IL-6 production at the post-translational level through histone acetylation.…”