Expression of SATB1 promotes the growth and metastasis of colorectal cancer

PLoS One. 2014 Jun 27;9(6):e100413. doi: 10.1371/journal.pone.0100413. eCollection 2014.

Abstract

Special AT-rich sequence-binding protein-1 (SATB1) has been identified as a genome organizer that reprograms chromatin organization and transcription profiles. SATB1 promotes tumor growth and metastasis in breast cancer and is associated with poor prognosis in several cancer types. The association between SATB1 and colorectal cancer (CRC) has not been studied intensively. Therefore, this study aimed to investigate the effect of SATB1 on CRC growth and metastasis in vitro and in vivo and its correlation with overall survival and clinicopathological factors in CRC patients. Stable SATB1 knockdown and SATB1-overexpressing cell lines were established. SATB1 knockdown decreased cell growth, colony formation, migration, and invasion and increased apoptosis in CRC cells in vitro (p<0.05), whereas SATB1 overexpression had the opposite effect. SATB1 overexpression increased tumor growth and metastasis to lung and liver in vivo by using xenograft animal models (p<0.05). Thus, SATB1 promoted an aggressive CRC phenotype in vitro and in vivo. Immunohistochemical analysis of 560 CRC specimens showed that SATB1 expression was significantly higher in CRC tissues than in matched non-tumor mucosa (p<0.001). In addition, SATB1 expression was significantly higher in patients with poorly differentiated tumors, higher invasion depth, distant metastasis, and advanced TNM stage. SATB1-positive patients had a poorer prognosis than SATB1-negative patients, and SATB1 was identified as an independent prognostic factor for CRC (p = 0.009). Strikingly, we also evaluated SATB2 expression in CRC and found that SATB2 was more abundantly expressed in non-cancerous mucosa compared to colorectal cancer tissues (p<0.001). However, SATB2 expression had no influence on prognosis of CRC patients (p = 0.836). SATB1 expression was significantly associated with shorter survival time either in SATB2-positive patients or in SATB2-negative patients (p<0.001). In conclusion, our findings indicated an important role for SATB1 in CRC tumorigenesis and metastasis. Therefore, SATB1 may represent an important prognostic biomarker and therapeutic target for CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Liver Neoplasms / secondary
  • Male
  • Matrix Attachment Region Binding Proteins / genetics*
  • Matrix Attachment Region Binding Proteins / metabolism
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Tumor Burden

Substances

  • Matrix Attachment Region Binding Proteins
  • RNA, Small Interfering
  • SATB1 protein, human

Grants and funding

This study was supported by National Natural Science funding (No: 81272765), Capital Characteristic Clinical Application Research (No: Z121107001012083), the Key Project of Capital Medical Development Fund (No: 2009-2095), Beijing Municipal Natural Science Foundation (No: 7122030), Beijing’s Outstanding Talents Subsidy Scheme (215 Program, No: 2009-2-18), Special Project of Beijing “Tens, Hundreds and Thousands” Health Talentsand funding from the Beijing Cancer Hospital (No: 10-04). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.