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TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior

Ai, Lingbao; Kim, Wan-Ju; Alpay, Merve; Tang, Ming; Pardo, Carolina E.; Hatakeyama, Shigetsugu; May, W. Stratford; Kladde, Michael P.; Heldermon, Coy D.; Siegel, Erin M.; Brown, Kevin D.


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{
  "DOI": "10.1158/0008-5472.CAN-13-3579", 
  "abstract": "TRIM29 (ATDC) exhibits a contextual function in cancer, but seems to exert a tumor-suppressor role in breast cancer. Here, we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial-mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene-expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival, increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT. (C) 2014 AACR.", 
  "author": [
    {
      "family": "Ai", 
      "given": " Lingbao"
    }, 
    {
      "family": "Kim", 
      "given": " Wan-Ju"
    }, 
    {
      "family": "Alpay", 
      "given": " Merve"
    }, 
    {
      "family": "Tang", 
      "given": " Ming"
    }, 
    {
      "family": "Pardo", 
      "given": " Carolina E."
    }, 
    {
      "family": "Hatakeyama", 
      "given": " Shigetsugu"
    }, 
    {
      "family": "May", 
      "given": " W. Stratford"
    }, 
    {
      "family": "Kladde", 
      "given": " Michael P."
    }, 
    {
      "family": "Heldermon", 
      "given": " Coy D."
    }, 
    {
      "family": "Siegel", 
      "given": " Erin M."
    }, 
    {
      "family": "Brown", 
      "given": " Kevin D."
    }
  ], 
  "container_title": "CANCER RESEARCH", 
  "id": "63399", 
  "issue": "17", 
  "issued": {
    "date-parts": [
      [
        2014, 
        1, 
        1
      ]
    ]
  }, 
  "page": "4875-4887", 
  "title": "TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior", 
  "type": "article-journal", 
  "volume": "74"
}
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