Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer
Abstract Background Ribosomal biogenesis and ribosomal proteins have attracted attention in the context of tumor biology in recent years. Instead of being mere translational machineries, ribosomes might play an active role in tumor initiation and progression. Despite its importance, regulation of ri...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-022-01562-8 |
| _version_ | 1817979641440239616 |
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| author | Anne-Marie Lüchtenborg Patrick Metzger Miguel Cosenza Contreras Victor Oria Martin L. Biniossek Franziska Lindner Klemens Fröhlich Ambrus Malyi Thalia Erbes Nicole Gensch Jochen Maurer Andreas Thomsen Melanie Boerries Oliver Schilling Martin Werner Peter Bronsert |
| author_facet | Anne-Marie Lüchtenborg Patrick Metzger Miguel Cosenza Contreras Victor Oria Martin L. Biniossek Franziska Lindner Klemens Fröhlich Ambrus Malyi Thalia Erbes Nicole Gensch Jochen Maurer Andreas Thomsen Melanie Boerries Oliver Schilling Martin Werner Peter Bronsert |
| author_sort | Anne-Marie Lüchtenborg |
| collection | DOAJ |
| description | Abstract Background Ribosomal biogenesis and ribosomal proteins have attracted attention in the context of tumor biology in recent years. Instead of being mere translational machineries, ribosomes might play an active role in tumor initiation and progression. Despite its importance, regulation of ribosomal biogenesis is still not completely understood. Methods Using Gene Set Enrichment Analysis of RNA sequencing and proteomical mass spectrometry data in breast cancer cells expressing Krüppel-like factor 7 (KLF7), we identified processes altered by this transcription factor. In silico analyses of a cohort of breast cancer patients in The Cancer Genome Atlas confirmed our finding. We further verified the role of KLF7 the identified ribosomal processes in in vitro assays of mammary carcinoma cell lines and analyses of breast cancer patients’ tissue slices. Results We identified the transcription factor Krüppel-like factor 7 (KLF7) as a regulator of ribosomal biogenesis and translation in breast cancer cells and tissue. Highly significant overlapping processes related to ribosomal biogenesis were identified in proteomics and transcriptomics data and confirmed in patients’ breast cancer RNA Seq data. Further, nucleoli, the sites of ribosomal biogenesis, were morphologically altered and quantitatively increased in KLF7-expressing cells. Pre-rRNA processing was identified as one potential process affected by KLF7. In addition, an increase in global translation independent from proliferation and transcription was observed upon exogenous KLF7 expression in vitro. Importantly, in a cohort of breast cancer patients, KLF7-expression levels correlated with aggressiveness of the intrinsic breast cancer subtype and tumor grading. Moreover, KLF7 correlated with nucleolar characteristics in human breast tumor tissue, indicating a role for KLF7 in ribosomal biogenesis. Conclusion In mammary carcinoma, KLF7 is involved in ribosomal biogenesis. Alterations of ribosomal biogenesis has far reaching quantitative and qualitative implications for the proteome of the cancer cells. This might influence the aggressiveness of cancer cells. |
| first_indexed | 2024-04-13T22:45:09Z |
| format | Article |
| id | doaj.art-fe86bccb7dfa47cca3bf5d88ffed6c71 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-04-13T22:45:09Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-fe86bccb7dfa47cca3bf5d88ffed6c712022-12-22T02:26:27ZengBMCBreast Cancer Research1465-542X2022-10-0124111510.1186/s13058-022-01562-8Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancerAnne-Marie Lüchtenborg0Patrick Metzger1Miguel Cosenza Contreras2Victor Oria3Martin L. Biniossek4Franziska Lindner5Klemens Fröhlich6Ambrus Malyi7Thalia Erbes8Nicole Gensch9Jochen Maurer10Andreas Thomsen11Melanie Boerries12Oliver Schilling13Martin Werner14Peter Bronsert15Institute for Surgical Pathology, Medical Center – University of FreiburgFaculty of Medicine, University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgFaculty of Biology, University of FreiburgInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgInstitute for Surgical Pathology, Medical Center – University of Freiburg2Nd Department of Pathology, Semmelweis UniversityDepartment of Obstetrics and Gynecology, Medical Center - University of FreiburgCore Facility Signaling Factory, BIOSS Centre for Biological Signaling Studies, University of FreiburgDepartment of Obstetrics and Gynecology, University Hospital Aachen (UKA)Department of Radiation Oncology, Medical Center – University of FreiburgFaculty of Medicine, University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgAbstract Background Ribosomal biogenesis and ribosomal proteins have attracted attention in the context of tumor biology in recent years. Instead of being mere translational machineries, ribosomes might play an active role in tumor initiation and progression. Despite its importance, regulation of ribosomal biogenesis is still not completely understood. Methods Using Gene Set Enrichment Analysis of RNA sequencing and proteomical mass spectrometry data in breast cancer cells expressing Krüppel-like factor 7 (KLF7), we identified processes altered by this transcription factor. In silico analyses of a cohort of breast cancer patients in The Cancer Genome Atlas confirmed our finding. We further verified the role of KLF7 the identified ribosomal processes in in vitro assays of mammary carcinoma cell lines and analyses of breast cancer patients’ tissue slices. Results We identified the transcription factor Krüppel-like factor 7 (KLF7) as a regulator of ribosomal biogenesis and translation in breast cancer cells and tissue. Highly significant overlapping processes related to ribosomal biogenesis were identified in proteomics and transcriptomics data and confirmed in patients’ breast cancer RNA Seq data. Further, nucleoli, the sites of ribosomal biogenesis, were morphologically altered and quantitatively increased in KLF7-expressing cells. Pre-rRNA processing was identified as one potential process affected by KLF7. In addition, an increase in global translation independent from proliferation and transcription was observed upon exogenous KLF7 expression in vitro. Importantly, in a cohort of breast cancer patients, KLF7-expression levels correlated with aggressiveness of the intrinsic breast cancer subtype and tumor grading. Moreover, KLF7 correlated with nucleolar characteristics in human breast tumor tissue, indicating a role for KLF7 in ribosomal biogenesis. Conclusion In mammary carcinoma, KLF7 is involved in ribosomal biogenesis. Alterations of ribosomal biogenesis has far reaching quantitative and qualitative implications for the proteome of the cancer cells. This might influence the aggressiveness of cancer cells.https://doi.org/10.1186/s13058-022-01562-8RibosomesKrüppel-like factor 7Transcription factorBreast cancerProteomicsTranscriptomics |
| spellingShingle | Anne-Marie Lüchtenborg Patrick Metzger Miguel Cosenza Contreras Victor Oria Martin L. Biniossek Franziska Lindner Klemens Fröhlich Ambrus Malyi Thalia Erbes Nicole Gensch Jochen Maurer Andreas Thomsen Melanie Boerries Oliver Schilling Martin Werner Peter Bronsert Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer Breast Cancer Research Ribosomes Krüppel-like factor 7 Transcription factor Breast cancer Proteomics Transcriptomics |
| title | Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer |
| title_full | Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer |
| title_fullStr | Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer |
| title_full_unstemmed | Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer |
| title_short | Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer |
| title_sort | kruppel like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer |
| topic | Ribosomes Krüppel-like factor 7 Transcription factor Breast cancer Proteomics Transcriptomics |
| url | https://doi.org/10.1186/s13058-022-01562-8 |
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