RNF4~RGMb~BMP6 axis required for osteogenic differentiation and cancer cell survival
Rostislav Novak,Yamen Abu Ahmad,Michael Timaner,Eliya Bitman-Lotan,Avital Oknin-Vaisman,Roi Horwitz,Oliver Hartmann,Michaela Reissland,Viktoria Buck,Mathias T. Rosenfeldt,David Nikomarov,Markus E. Diefenbacher,Yuval Shaked,Amir Orian +13 more
Reads0
Chats0
TLDR
In this article , the RNF4 ubiquitin ligase is essential for osteogenic differentiation (OD) of human bone marrow-derived mesenchymal stem cells (hBMSCs).Abstract:
Molecular understanding of osteogenic differentiation (OD) of human bone marrow-derived mesenchymal stem cells (hBMSCs) is important for regenerative medicine and has direct implications for cancer. We report that the RNF4 ubiquitin ligase is essential for OD of hBMSCs, and that RNF4-deficient hBMSCs remain as stalled progenitors. Remarkably, incubation of RNF4-deficient hBMSCs in conditioned media of differentiating hBMSCs restored OD. Transcriptional analysis of RNF4-dependent gene signatures identified two secreted factors that act downstream of RNF4 promoting OD: (1) BMP6 and (2) the BMP6 co-receptor, RGMb (Dragon). Indeed, knockdown of either RGMb or BMP6 in hBMSCs halted OD, while only the combined co-addition of purified RGMb and BMP6 proteins to RNF4-deficient hBMSCs fully restored OD. Moreover, we found that the RNF4-RGMb-BMP6 axis is essential for survival and tumorigenicity of osteosarcoma and therapy-resistant melanoma cells. Importantly, patient-derived sarcomas such as osteosarcoma, Ewing sarcoma, liposarcomas, and leiomyosarcomas exhibit high levels of RNF4 and BMP6, which are associated with reduced patient survival. Overall, we discovered that the RNF4~BMP6~RGMb axis is required for both OD and tumorigenesis. read more
Citations
More filters
Journal ArticleDOI
USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer
Carina R. Maier,Oliver Hartmann,Cristian Prieto-Garcia,Kamal M Al-Shami,Lisa Schlicker,Felix C. E. Vogel,Kevin Klann,Viktoria Buck,Christian Münch,Werner Schmitz,Elias Einig,Bastian Krenz,Marco A. Calzado,Martin Eilers,Nikita Popov,Mathias T. Rosenfeldt,Markus E. Diefenbacher,Almut Schulze +17 more
TL;DR: In this paper , the authors identify SREBP2 as a novel substrate for USP28, a deubiquitinating enzyme that is frequently upregulated in squamous cancers.
Posted ContentDOI
IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells
TL;DR: In this article , the IL-1R-associated kinase 4 (IRAK4) inhibition was reported to antagonize inflammatory osteolysis and reciprocally regulate osteoclasts and foreign body giant cells (FBGCs), which may be a potential target in implant osseointegration.
Journal ArticleDOI
IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells
TL;DR: In this article , the IL-1R-associated kinase 4 (IRAK4) inhibition was reported to antagonize inflammatory osteolysis and regulate osteoclasts and foreign body giant cells (FBGCs).
References
More filters
Journal ArticleDOI
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
Journal ArticleDOI
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks
Paul Shannon,Andrew Markiel,Owen Ozier,Nitin S. Baliga,Jonathan T. Wang,Daniel Ramage,Nada Amin,Benno Schwikowski,Trey Ideker +8 more
TL;DR: Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
Posted ContentDOI
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
Journal ArticleDOI
The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data
Ethan Cerami,Jianjiong Gao,Ugur Dogrusoz,Benjamin Gross,Selcuk Onur Sumer,Bulent Arman Aksoy,Anders Jacobsen,Caitlin Byrne,Michael Heuer,Erik G. Larsson,Yevgeniy Antipin,Boris Reva,Arthur P. Goldberg,Chris Sander,Nikolaus Schultz +14 more
TL;DR: The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications.
Journal ArticleDOI
Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal
Jianjiong Gao,Bulent Arman Aksoy,Ugur Dogrusoz,Gideon Dresdner,Benjamin Gross,S. Onur Sumer,Yichao Sun,Anders Jacobsen,Rileen Sinha,Erik Larsson,Ethan Cerami,Chris Sander,Nikolaus Schultz +12 more
TL;DR: A practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics, which makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries.
Related Papers (5)
CRISPR-Cas13d Induces Efficient mRNA Knockdown in Animal Embryos.
Gopal Kushawah,Luis Hernandez-Huertas,Joaquin Abugattas-Nuñez del Prado,Joaquin Abugattas-Nuñez del Prado,Juan R. Martinez-Morales,Michelle Lynn DeVore,Huzaifa Hassan,Ismael Moreno-Sanchez,Laura Tomas-Gallardo,Alejandro Díaz-Moscoso,Dahiana E. Monges,Javier R. Guelfo,William C. Theune,Emry O. Brannan,Wei Wang,Timothy J. Corbin,Andrea Moran,Alejandro Sánchez Alvarado,Edward Málaga-Trillo,Carter M. Takacs,Ariel A. Bazzini,Ariel A. Bazzini,Miguel A. Moreno-Mateos +22 more