SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis

Han, Hye‐Jung; Russo, José; Kohwi, Yoshinori; Kohwi‐Shigematsu, Terumi

doi:10.1038/nature06781

Cited by 465 publications

(696 citation statements)

References 48 publications

Supporting

Mentioning

645

Contrasting

Unclassified

Order By: Relevance

“…It reprogrammes chromatin organization and the transcription profiles of breast tumors to act as a determinant of morphogenesis and metastasis. 29 Herein, an inverse correlation was found between miR-448 and SATB1 in drug-treated breast cancer cell lines, in post-chemotherapy human breast samples, and in tumorimplanted mice. We proposed that miR-448 suppression is pivotal in the process of chemotherapy-induced EMT.…”

Section: Discussionmentioning

confidence: 97%

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

et al. 2010

Cell Death Differ

166

127

View full text Add to dashboard Cite

The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor jB (NF-jB) activation. On the other hand, we also found that the adriamycin-activated NF-jB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-jB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-jB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-jB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component. Chemotherapy is a systemic treatment that destroys reproducing cells, but it cannot differentiate between normal and cancerous cells. Side effects occur when normal cells become damaged. Apart from the side effects of cancer chemotherapy, unexpected 'opposite effects' of chemotherapy, which enhance the critical steps in malignancy rather than inhibiting them, 1-3 have attracted progressively more attention, suggesting that novel strategies should be developed to reverse these opposite effects and render chemotherapy more effective.Tumor cells progress from non-invasive to malignant phenotypes via a series of critical steps that involve morphological changes referred to as the epithelial-mesenchymal transition (EMT). 4 EMT is a process originally observed during the embryonic development, in which cells lose epithelial characteristics. [5][6][7][8][9][10] With respect to the chemotherapy, recent studies have demonstrated a close link between EMT and insensitivity to chemotherapeutic agents. Hiscox et al. 11 showed increased b-catenin expression and elevated levels of transcription of b-catenin target genes known to be involved in tumor progression and EMT in the tamoxifen (TAM)-resistant MCF7 cells. Kajiyama et al. 12 identified an association between chronic paclitaxel resistance and induction of EMT in epithelial ovarian carcinomas. In addition, we previously showed that transient adriamycin treatmentinduced EMT and apoptosi...

show abstract

Section: Discussionmentioning

confidence: 97%

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

et al. 2010

Cell Death Differ

166

127

View full text Add to dashboard Cite

show abstract

“…We found ATrich sequences being a strong positive predictor in all of the calculated models. Recently, it was reported that SATB1, the special AT-rich binding protein, is highly expressed in aggressive breast cancer cells (40). SATB1 belongs to a family of nuclear matrix binding proteins, which constitute and maintain the DNA nuclear architecture, thereby regulating cell-specific gene expression.…”

Section: Discussionmentioning

confidence: 99%

Next Generation Sequencing of Serum Circulating Nucleic Acids from Patients with Invasive Ductal Breast Cancer Reveals Differences to Healthy and Nonmalignant Controls

Beck

Urnovitz

Mitchell

et al. 2010

Molecular Cancer Research

View full text Add to dashboard Cite

Circulating nucleic acids (CNA) isolated from serum or plasma are increasingly recognized as biomarkers for cancers. Recently developed next generation sequencing provides high numbers of DNA sequences to detect the trace amounts of unique serum biomarkers associated with breast carcinoma. Serum CNA of 38 women with ductal carcinoma was extracted and sequenced on a 454/Roche high-throughput GS-FLX platform and compared with healthy controls and patients with other medical conditions. Repetitive elements present in CNA were detected and classified, and each repetitive element was normalized based on total sequence count or repeat count. Multivariate regression models were calculated using an information-theoretical approach and multimodel inference. A total of 423,150 and 953,545 sequences for the cancer patients and controls, respectively, were obtained. Data from 26 patients with stages II to IV tumors and from 67 apparently healthy female controls were used as the training data set. Using a bootstrap method to avoid sampling bias, a five-parameter model was developed. When this model was applied to a validation data set consisting of patients with tumor stage I (n = 10) compared with healthy and nonmalignant disease controls (n = 87; 1,261,561 sequences) a sensitivity of 70% at a specificity of 100% was obtained. At a diagnostic specificity level of 95%, a sensitivity of 90% was calculated. Identification of specific breast cancer-related CNA sequences provides the basis for the development of a serum-based routine laboratory test for breast cancer screening and monitoring.

show abstract

“…In primary breast tumours, high SATB1 expression was found to correlate with aggressiveness and poor clinical outcome, irrespective of lymph node status, enabling it to be considered as an independent breast cancer marker. As breast tumour growth and metastasis in mice could be prevented using RNA interference against SATB1, the protein is a potential novel target for therapy [64].…”

Section: The Role Of Nuclear Organization In Cancer 119mentioning

confidence: 99%

The role of nuclear organization in cancer

Lever¹,

Sheer²

2009

The Journal of Pathology

View full text Add to dashboard Cite

The functional significance of changes in nuclear structure and organization in transformed cells remains one of the most enigmatic questions in cancer biology. In this review, we discuss relationships between nuclear organization and transcription in terms of the threedimensional arrangement of genes in the interphase cancer nucleus and the regulatory functions of nuclear matrix proteins. We also analyse the role of nuclear topology in the generation of gene fusions. We speculate that this type of multi-layered analysis will one day provide a framework for a more comprehensive understanding of the genetic origins of cancer and the identification of new therapeutic targets.

show abstract

SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis

Cited by 465 publications

References 48 publications

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

Next Generation Sequencing of Serum Circulating Nucleic Acids from Patients with Invasive Ductal Breast Cancer Reveals Differences to Healthy and Nonmalignant Controls

The role of nuclear organization in cancer

Contact Info

Product

Resources

About