Correlation of SATB1 overexpression with the progression of human rectal cancer

Wei, Meng; Yan, Hui; Zhou, Bin; Zhang, Wei; Kong, XiangHeng; Wang, Rong; Zhan, Lisi; Li, Yuan; Zhou, Zong-Guang; Sun, Xiaoying

doi:10.1007/s00384-011-1302-9

Cited by 69 publications

(99 citation statements)

References 19 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].…”

Section: Discussioncontrasting

confidence: 74%

“…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: 48%

“…Meng et al found that SATB1 protein expression in tumour samples from rectal cancer patients correlated with increasing tumour stage and tumour depth of invasion [2]. 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].…”

Section: Introductionmentioning

confidence: 84%

“…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: 74%

Section: Discussionsupporting

confidence: 48%

Section: Introductionmentioning

confidence: 84%

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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SATB1, senescence and senescence‐related diseases

Qi,

Bai,

Wang

et al. 2024

Journal Cellular Physiology

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Aging leads to an accumulation of cellular mutations and damage, increasing the risk of senescence, apoptosis, and malignant transformation. Cellular senescence, which is pivotal in aging, acts as both a guard against cellular transformation and as a check against cancer progression. It is marked by stable cell cycle arrest, widespread macromolecular changes, a pro‐inflammatory profile, and altered gene expression. However, it remains to be determined whether these differing subsets of senescent cells result from unique intrinsic programs or are influenced by their environmental contexts. Multiple transcription regulators and chromatin modifiers contribute to these alterations. Special AT‐rich sequence‐binding protein 1 (SATB1) stands out as a crucial regulator in this process, orchestrating gene expression by structuring chromatin into loop domains and anchoring DNA elements. This review provides an overview of cellular senescence and delves into the role of SATB1 in senescence‐related diseases. It highlights SATB1's potential in developing antiaging and anticancer strategies, potentially contributing to improved quality of life and addressing aging‐related diseases.

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Correlation of SATB1 overexpression with the progression of human rectal cancer

Abstract: Background and aims To date, the association between special AT-rich sequence-binding protein 1

Cited by 69 publications

References 19 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

SATB1, senescence and senescence‐related diseases

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