Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer

Xinyu Wu, Yang Zhan, Xin Li, Jianjun Wei, Larion Santiago, Garrett Daniels, Fangming Deng, Xuelin Zhong, Luis Chiriboga, Ross Basch, Sheng Xiong, Yan Dong, Xinmin Zhang, Peng Lee

Research output: Contribution to journalArticle

Abstract

Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells. TBLR1 functions as an ER corepressor to inhibit ER-mediated transcriptional activation in both breast and ovarian cell lines, but it has no effect on androgen receptor (AR) mediated transcriptional activation in these cells. Furthermore, ectopic expression of nuclear TBLR1 in breast and ovarian cancer cells stimulates cell proliferation. The increased cell proliferation by nuclear TBLR1 is through both ER-independent and ER-dependent mechanisms as evidenced by increased growth in hormone-free medium and estrogen medium, as well as reduced growth with ER knockdown by siRNA. Nuclear TBLR1 overexpression also increased migration and invasion in both breast and ovarian cancer cells. Determining the functional relationship between TBLR1 and ER may provide insights to develop novel treatment strategies and improve response to hormonal therapy in breast and ovarian cancers.

Original languageEnglish (US)
Pages (from-to)2351-2360
Number of pages10
JournalAmerican Journal of Cancer Research
Volume6
Issue number10
StatePublished - Jan 1 2016

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Keywords

  • Breast cancer
  • Estrogen receptor
  • Nuclear TBLR1
  • Ovarian cancer
  • TBL1XR1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wu, X., Zhan, Y., Li, X., Wei, J., Santiago, L., Daniels, G., Deng, F., Zhong, X., Chiriboga, L., Basch, R., Xiong, S., Dong, Y., Zhang, X., & Lee, P. (2016). Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer. American Journal of Cancer Research, 6(10), 2351-2360.