Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer

Nodin, Björn; Johannesson, Henrik; Wangefjord, Sakarias; O’Connor, Darran P.; Lindquist, Kajsa Ericson; Uhlén, Mathias; Jirström, Karin; Eberhard, Jakob

doi:10.1186/1746-1596-7-115

Cited by 56 publications

(91 citation statements)

References 26 publications

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“…The Meng et al and Zhang et al studies observed a correlation of SATB1 protein expression with advanced disease stage and increased tumor depth of invasion [2,4]. However, both the Nodin et al and our study did not show any correlation indicative of a poorer disease outcome of SATB1 expression with patient characteristics [3]. There were also correlations with certain patient characteristics observed by one group but not seen by the other researchers, such as gender [3] and tumor differentiation grade [4].…”

Section: Discussioncontrasting

confidence: 54%

“…The SATB1 protein expression frequencies in CRC in these reports vary between 42% -59%. In normal colonic mucosa these frequencies varied between 3% -26% [2][3][4]. In our study, we observed a frequency of approximately 18% in cancerous tissues and a relatively high frequency of 52% in normal tissues.…”

Section: Discussionsupporting

confidence: 49%

“…This finding was validated by Zhang et al who further found that down regulation of SATB1 in a CRC cell line led to decreased proliferation, increased apoptosis and reduced invasion [4]. Contradictory to these findings, Nodin et al found no correlation with clinico-pathological characteristics, but did observe a correlation of SATB1 expression with poorer cancer related survival within a specific CRC subgroup [3]. Since the protein's exact role in colorectal cancer is as yet unclear, we decide to further investigate this subject.…”

Section: Introductionsupporting

confidence: 55%

“…Alternatively it can also be explained by the use of different antibodies and differences in the applied methodologies and interpretation of the results. Regarding this, we used the same antibody as the Zhang et al study [4], while the Nodin et al and Meng et al studies shared a different antibody [2,3]. Also, the scoring system we applied is likely the least stringent of the four methods used, which would account for the relatively high expression frequency for SATB1 seen in the normal mucosa samples.…”

Section: Discussionmentioning

confidence: 99%

“…There is currently a great search for predictive and targetable biomarkers in CRC. The nuclear protein SATB1 might be involved in some of the molecular mechanisms that contribute to more aggressive CRC phenotypes [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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SATB1 Protein Is Associated with a More Aggressive Phenotype of Sporadic Colorectal Cancer

Davelaar¹,

Rygiel²,

Timmer³

et al. 2013

OJPathology

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Objective: SATB1 is a genome organizer known for its role in T-cell development. With its cage-like, nuclear architecture regulates a number of genes through epigenetic modifications. Ectopic expression of SATB1 has been shown to enhance aggressive behaviour of cancer. Here, we investigated whether this putative function can also be detected in sporadic colorectal cancer. Material and Methods: SATB1 protein expression in 107 cancer samples was screened using immunohistochemistry on tissue microarrays. These stainings were evaluated with respect to clinico-pathological parameters and patient outcome. In functional assays on cell lines, association of SATB1 with tumour cell behaviour was investigated. Results: Nuclear expression of SATB1 was seen in 17.8% of the cancers. A significantly poorer disease-free survival was seen in patients positive for SATB1 expression (Log-rank test, p = 0.003). Cox regression analysis showed that SATB1 expression (p = 0.009, RR = 3.6, 95% CI = 1.4 to 9.4) was an independent predictor of disease relapse. Knockdown and ectopic expression of SATB1 in colorectal cancer cell lines lead to a corresponding decrease and increase in the migratory and invasive capacity of the respective cells. Conclusions: In colorectal cancer, nuclear expression of SATB1 correlates with a more aggressive disease. This reflects in the accompanying increased risk of disease relapse.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionsupporting

confidence: 49%

Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

SATB1 Protein Is Associated with a More Aggressive Phenotype of Sporadic Colorectal Cancer

Davelaar¹,

Rygiel²,

Timmer³

et al. 2013

OJPathology

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Multiple effects of the special AT‐rich binding protein 1 (SATB1) in colon carcinoma

Frömberg

Rabe

Aigner

2014

Intl Journal of Cancer

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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, b-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.Colorectal cancer (CRC) is one of the most common causes for cancer-related deaths in the Western world. 1 Although methods of diagnosis and treatment have improved over the last few decades, the tumor stage at diagnosis is still most important for prognosis, and the overall survival of patients with advanced CRC is still poor owing to the high risk of metastasis. 2 The special AT-rich binding protein 1 (SATB1) is a global chromatin organizer that regulates the expression of a large number of genes. 3 SATB1 interacts with the altered sugarphosphate backbone of the DNA that is specific for doublestranded base-unpairing regions (BURs). BURs are often found in matrix attachment regions (MARs) at the base of chromatin loops. 4 In the nuclei of thymocytes, SATB1 has a cage-like network distribution and tethers specialized DNA sequences onto its network. 5 Furthermore, SATB1 targets chromatin remodeling complexes to DNA at the base of chromatin loops, functioning as a "landing platform" for chromatin remodeling enzymes. 6 In this way, SATB1 folds chromatin into loops and regulates the expression of a multitude of genes in cell type-and cell function-specific manners. 5,7-10 Under physiological conditions, SATB1 is required for the development of thymocytes 8 and the activation of Th2 cells. 7 Furthermore, SATB1 participates in Xchromosome inactivation, 11 development...

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Retracted: MiR‐191‐5p inhibits lung adenocarcinoma by repressing SATB1 to inhibit Wnt pathway

Zhou

Zhang

Tong

et al. 2019

Molec Gen & Gen Med

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Background To investigate the function of miR‐191‐5p in lung adenocarcinoma and its possible mechanism. Methods QRT‐PCR was adopted for the detection of the expression levels of miR‐191‐5p and SATB1 (HGNC: 10541). The effects of miR‐191‐5p and SATB1 on cell proliferation and migration were examined through the CCK‐8 and Transwell assays. Subsequently, the binding relationships between miR‐191‐5p and SATB1 were confirmed by dual‐luciferase reporter gene assay. Finally, the potential mechanisms of action of miR‐191‐5p were explored through a serious of in vivo and in vitro experiments. Results Lung adenocarcinoma patients had a notably lower expression level of miR‐191‐5p than controls, patients with metastasis had a lower level than those without metastasis, and the level in patients with lung adenocarcinoma in stage III‐IV was lower than that in patients with lung adenocarcinoma in stage I‐II. Overexpression of miR‐191‐5p repressed the migration and proliferation of lung cancer A549/H1650 cells. According to the reporter gene assay, miR‐191‐5p could bind to SATB1. Besides, SATB1 was significantly overexpressed in cancer tissues of patients with lung adenocarcinoma, and SATB1 overexpression accelerated the migration and proliferation of A549/H1650 cells and reversed inhibition on cell migration and proliferation by miR‐191‐5p. Conclusion Overexpression of miR‐191‐5p is capable of blocking the migration and proliferation of lung cancer cells, and its mechanism may be through targeting SATB1 thus downregulating Wnt signaling.

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Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer

Cited by 56 publications

References 26 publications

SATB1 Protein Is Associated with a More Aggressive Phenotype of Sporadic Colorectal Cancer

SATB1 Protein Is Associated with a More Aggressive Phenotype of Sporadic Colorectal Cancer

Multiple effects of the special AT‐rich binding protein 1 (SATB1) in colon carcinoma

Retracted: MiR‐191‐5p inhibits lung adenocarcinoma by repressing SATB1 to inhibit Wnt pathway

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