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PRH/Hhex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin

Research output: Contribution to journalArticle

  • Rachel Kershaw
  • Yusra Siddiqui
  • Dan Roberts
  • P Jayaraman
  • Kevin Gaston
Original languageEnglish
Pages (from-to)5592-5600
Number of pages9
JournalOncogene
Volume33
Issue number49
Early online date18 Nov 2013
DOIs
DateAccepted/In press - 11 Oct 2013
DateE-pub ahead of print - 18 Nov 2013
DatePublished (current) - 2014

Abstract

PRH/HHex (proline-rich homeodomain protein) is a transcription factor that controls cell proliferation and cell differentiation in a variety of tissues. Aberrant subcellular localisation of PRH is associated with breast cancer and thyroid cancer. Further, in blast crisis chronic myeloid leukaemia, and a subset of acute myeloid leukaemias, PRH is aberrantly localised and its activity is downregulated. Here we show that PRH is involved in the regulation of cell migration and cancer cell invasion. We show for the first time that PRH is expressed in prostate cells and that a decrease in PRH protein levels increases the migration of normal prostate epithelial cells. We show that a decrease in PRH protein levels also increases the migration of normal breast epithelial cells. Conversely, PRH overexpression inhibits cell migration and cell invasion by PC3 and DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. Previous work has shown that the transforming growth factor-β co-receptor Endoglin inhibits the migration of prostate and breast cancer cells. Here we show that PRH can bind to the Endoglin promoter in immortalised prostate and breast cells. PRH overexpression in these cells results in increased Endoglin protein expression, whereas PRH knockdown results in decreased Endoglin protein expression. Moreover, we demonstrate that Endoglin overexpression abrogates the increased migration shown by PRH knockdown cells. Our data suggest that PRH controls the migration of multiple epithelial cell lineages in part at least through the direct transcriptional regulation of Endoglin. We discuss these results in terms of the functions of PRH in normal cells and the mislocalisation of PRH seen in multiple cancer cell types.

    Research areas

  • HHex, PRH, cell migration, invasion, breast cancer, prostate cancer

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via SpringerNature at http://www.nature.com/onc/journal/v33/n49/full/onc2013496a.html?foxtrotcallback=true. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 589 KB, PDF-document

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