Special AT-rich sequence binding protein 1 regulates the multidrug resistance and invasion of human gastric cancer cells.

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as a global chromatin organizer to regulate gene expression. Recent studies have suggested an oncogenic role of SATB1 in breast cancer. However, the role of SATB1 in gastric cancer, especially in regulating the malignant phenotypes, including multidrug resistance (MDR) and metastasis, remains poorly understood. In this study, the aggressive human gastric cancer cell line SGC7901 and its corresponding MDR variant SGC7901/VCR cells were used as a model. SATB1 expression was examined by RT-PCR and western blot analysis. Results showed that SATB1 was upregulated in SGC7901/VCR cells. An in vitro drug sensitivity assay demonstrated a positive correlation between SATB1 expression levels and drug resistance. Gain and loss of SATB1 function experiments further demonstrated that SATB1 contributes to MDR by inhibiting the accumulation of vincristine (VCR) in gastric cancer cells and protecting the cells from VCR-induced apoptosis. In addition, SATB1 may promote the invasion of gastric cancer cells. The present study provides a novel insight into the oncogenic role of SATB1 in gastric cancer, suggesting that SATB1 is a promising target for the therapy of drug-resistant and invasive gastric cancer.

[1]  H. Niida,et al.  The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. , 2000, Genes & development.

[2]  J. Bertino,et al.  Drug resistance in colon cancer. , 1999, Seminars in oncology.

[3]  Qiang Yu,et al.  Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells. , 2002, Cancer letters.

[4]  M. Gottesman,et al.  Multidrug resistance in cancer: role of ATP–dependent transporters , 2002, Nature Reviews Cancer.

[5]  S. Maxwell,et al.  Biological and molecular characterization of an ECV-304-derived cell line resistant to p53-mediated apoptosis , 2000, Apoptosis.

[6]  M. Caraglia,et al.  The multidrug transporter P-glycoprotein: a mediator of melanoma invasion? , 2008, The Journal of investigative dermatology.

[7]  Jie Zheng.  Is SATB1 a Master Regulator in Breast Cancer Growth and Metastasis? , 2008, Women's health.

[8]  A. Yokomizo,et al.  Mechanisms of drug resistance in chemotherapy for urogenital carcinoma , 1999, International journal of urology : official journal of the Japanese Urological Association.

[9]  Y. Kohwi,et al.  A tissue-specific MAR SAR DNA-binding protein with unusual binding site recognition , 1992, Cell.

[10]  T. Kohwi-Shigematsu,et al.  Tissue-specific nuclear architecture and gene expession regulated by SATB1 , 2003, Nature Genetics.

[11]  Saraswati Sukumar,et al.  Distant Metastasis in Breast Cancer: Molecular Mechanisms and Therapeutic Targets , 2003, Cancer biology & therapy.

[12]  T. Kohwi-Shigematsu,et al.  SATB1 targets chromatin remodelling to regulate genes over long distances , 2002, Nature.

[13]  G. Z. Cheng,et al.  Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. , 2007, Cancer research.

[14]  Yumei Zhang,et al.  Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis. , 2004, Experimental cell research.

[15]  D. Spector,et al.  The dynamics of chromosome organization and gene regulation. , 2003, Annual review of biochemistry.

[16]  Xiaohua Li,et al.  CIAPIN1 confers multidrug resistance by upregulating the expression of MDR-1 and MRP-1 in gastric cancer cells , 2006, Cancer biology & therapy.

[17]  J. Russo,et al.  SATB 1 reprogrammes gene expression to promote breast tumour growth and metastasis , 2008 .

[18]  David C. Smith,et al.  Advances in Prostate Cancer Chemotherapy: A New Era Begins 1 , 2005, CA: a cancer journal for clinicians.

[19]  Qing-quan Li,et al.  Overexpression and involvement of special AT‐rich sequence binding protein 1 in multidrug resistance in human breast carcinoma cells , 2010, Cancer science.

[20]  Q. Tong,et al.  SATB1 is an independent prognostic marker for gastric cancer in a Chinese population. , 2010, Oncology reports.

[21]  Xiaoyan Jiang,et al.  Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription. , 2011, Blood.

[22]  Jin-Ming Yang,et al.  Involvement of CD147 in regulation of multidrug resistance to P‐gp substrate drugs and in vitro invasion in breast cancer cells , 2007, Cancer science.

[23]  R. Mumper,et al.  Nanomedicinal strategies to treat multidrug-resistant tumors: current progress. , 2010, Nanomedicine.

[24]  I. Mian,et al.  A Nuclear Targeting Determinant for SATB1, a Genome Organizer in the T Cell Lineage , 2005, Cell cycle.

[25]  T. Ozben.  Mechanisms and strategies to overcome multiple drug resistance in cancer , 2006, FEBS letters.

[26]  L. Kenner,et al.  SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. , 2009, Developmental cell.

[27]  T. Kohwi-Shigematsu,et al.  Articles on similar topics can be found in the following Blood collections Gene Expression (1086 articles) , 2004 .