NDLI: Krüppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer

Content Provider	Springer Nature : BioMed Central
Author	Lüchtenborg, Anne-Marie Metzger, Patrick Cosenza Contreras, Miguel Oria, Victor Biniossek, Martin L. Lindner, Franziska Fröhlich, Klemens Malyi, Ambrus Erbes, Thalia Gensch, Nicole Maurer, Jochen Thomsen, Andreas Boerries, Melanie Schilling, Oliver Werner, Martin Bronsert, Peter
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.
Related Links	https://breast-cancer-research.biomedcentral.com/counter/pdf/10.1186/s13058-022-01562-8.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13058-022-01562-8
Journal	Breast Cancer Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2022-10-03
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Ribosomes Krüppel-like factor 7 Transcription factor Breast cancer Proteomics Transcriptomics Nucleoli
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7.1/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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