TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence

Lucy Cassar, Craig Nicholls, Alex R. Pinto, Ruping Chen, Lihui Wang, He Li, Jun Ping Liu

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene.

Original languageEnglish
Pages (from-to)39-54
Number of pages16
JournalProtein & Cell
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • BMPRII
  • breast cancer cells
  • hTERT
  • senescence
  • telomerase
  • telomeres
  • TGFbeta

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