TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence
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) ind...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2016-09-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-016-0322-1 |
| _version_ | 1827883511922556928 |
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| author | Lucy Cassar Craig Nicholls Alex R. Pinto Ruping Chen Lihui Wang He Li Jun-Ping Liu |
| author_facet | Lucy Cassar Craig Nicholls Alex R. Pinto Ruping Chen Lihui Wang He Li Jun-Ping Liu |
| author_sort | Lucy Cassar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:14:33Z |
| format | Article |
| id | doaj.art-ec2417c9aa2e4be2bbbeb97463a55165 |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T19:14:33Z |
| publishDate | 2016-09-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-ec2417c9aa2e4be2bbbeb97463a551652023-08-02T05:38:36ZengOxford University PressProtein & Cell1674-800X1674-80182016-09-0181395410.1007/s13238-016-0322-1TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescenceLucy Cassar0Craig Nicholls1Alex R. Pinto2Ruping Chen3Lihui Wang4He Li5Jun-Ping Liu6Molecular Signaling Laboratory, Department of Immunology, Central Eastern Clinical School, Monash UniversityMolecular Signaling Laboratory, Department of Immunology, Central Eastern Clinical School, Monash UniversityMolecular Signaling Laboratory, Department of Immunology, Central Eastern Clinical School, Monash UniversityInstitute of Aging Research, Hangzhou Normal University School of MedicineInstitute of Aging Research, Hangzhou Normal University School of MedicineMolecular Signaling Laboratory, Department of Immunology, Central Eastern Clinical School, Monash UniversityMolecular Signaling Laboratory, Department of Immunology, Central Eastern Clinical School, Monash UniversityABSTRACT 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.http://link.springer.com/article/10.1007/s13238-016-0322-1BMPRIITGFbetahTERTtelomerasetelomeressenescence |
| spellingShingle | Lucy Cassar Craig Nicholls Alex R. Pinto Ruping Chen Lihui Wang He Li Jun-Ping Liu TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence Protein & Cell BMPRII TGFbeta hTERT telomerase telomeres senescence |
| title | TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence |
| title_full | TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence |
| title_fullStr | TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence |
| title_full_unstemmed | TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence |
| title_short | TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence |
| title_sort | tgf beta receptor mediated telomerase inhibition telomere shortening and breast cancer cell senescence |
| topic | BMPRII TGFbeta hTERT telomerase telomeres senescence |
| url | http://link.springer.com/article/10.1007/s13238-016-0322-1 |
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