Abstract
Mutations in numerous genes contribute to human cancer, with different oncogenic lesions prevalent in different cancer types. However, the malignant phenotype is simple, characterized by unrestricted cell growth, invasion, and often metastasis. One possible hypothesis explaining this dichotomy is that cancer genes regulate common targets, which then function as master regulators of essential cancer phenotypes. To identify mechanisms that drive the most fundamental feature shared by all tumors—unrestricted cell proliferation—we used a multiomic approach, which identified translation and ribosome biogenesis as common targets of major oncogenic pathways across cancer types. Proteomic analysis of tumors and functional studies of cell cultures established nucleolar and coiled-body phosphoprotein 1 as a key node, whose convergent regulation, both transcriptionally and posttranslationally, is critical for tumor cell proliferation. Our results indicate that lineage-specific oncogenic pathways regulate the same set of targets for growth control, revealing key downstream nodes that could be targeted for therapy or chemoprevention.
| Original language | English |
|---|---|
| Article number | eadt1798 |
| Journal | Science Advances |
| Volume | 11 |
| Issue number | 34 |
| DOIs | |
| Publication status | Published - 22 Aug 2025 |
| MoE publication type | A1 Journal article-refereed |
Funding
We thank Q. Zhang and S. Miettinen for technical assistance, K. Kurppa for critical review of the manuscript, and J. Klefström for valuable suggestions. Tumor proteomics analyses were performed at the Turku Proteomics Facility, University of Turku, and Åbo Akademi University. The facility is supported by Biocenter Finland. We thank the Sequencing Unit of Institute for Molecular Medicine Finland FIMM Technology Centre and Biomedicum Functional Genomics Unit (FuGU) at University of Helsinki for sequencing and microarray services. FIMM Sequencing Unit is supported by Biocenter Finland. The Chemical Proteomics core facility at Biomedicum (MBB, Karolinska Institute), also the Unit of SciLifeLab and part of the Swedish National Infrastructure for Biological Mass Spectrometry (BioMS), provided full support in the experimental design and performance of the proteomics using the PISA assay, with relative data analysis. This work was supported by following grants: Academy of Finland, Finnish Center of Excellence program: 2012–2017 (250345) and 2018–2025 (312042) (J.T.); Cancer Foundation Finland (J.T.); Cancer Research UK grant C55958/ A28801/RG99643 (J.T.); Swedish Research Council D0815201 (J.T.); Finnish medical foundation grant 3977 (O.K.); Cancer Foundation Finland 61-5961 (O.K.); Academy of Finland 288836 (P.P.); European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 965193 (DECIDER) (S.H.); and Academy of Finland projects 325956 and 322927 (S.H. and A.H.) Acknowledgments: We thank Q. Zhang and S. Miettinen for technical assistance, K. Kurppa for critical review of the manuscript, and J. Klefström for valuable suggestions. tumor proteomics analyses were performed at the turku Proteomics Facility, University of turku, and Åbo Akademi University. the facility is supported by Biocenter Finland. We thank the Sequencing Unit of institute for Molecular Medicine Finland FiMM technology centre and Biomedicum Functional Genomics Unit (FuGU) at University of helsinki for sequencing and microarray services. FiMM Sequencing Unit is supported by Biocenter Finland. the chemical Proteomics core facility at Biomedicum (MBB, Karolinska institute), also the Unit of Scilifelab and part of the Swedish national infrastructure for Biological Mass Spectrometry (BioMS), provided full support in the experimental design and performance of the proteomics using the PiSA assay, with relative data analysis. Funding: this work was supported by following grants: Academy of Finland, Finnish center of excellence program: 2012–2017 (250345) and 2018–2025 (312042) (J.t.); cancer Foundation Finland (J.t.); cancer Research UK grant c55958/ A28801/RG99643 (J.t.); Swedish Research council d0815201 (J.t.); Finnish medical foundation grant 3977 (O.K.); cancer Foundation Finland 61-5961 (O.K.); Academy of Finland 288836 (P.P.); european Union’s horizon 2020 Research and innovation Programme under grant agreement no. 965193 (decideR) (S.h.); and Academy of Finland projects 325956 and 322927 (S.h. and A.h.) Author contributions: conceptualization: O.K., J.t., M.t., J.l.G., and S.v. investigation: O.K., J.t., M.t., P.P., A.h., K.S.l., M.P., S.v., M.G., S.l.l., B.S., J.R., t.K., G.-h.W., h.i., and S.h. Methodology: O.K., J.t., R.M.l.Q., K.S.l., M.t., A.M., J.l.G., A.h., M.G., and S.v. Formal analysis: O.K., J.t., t.K., G.-h.W., S.l.l., J.l.G., P.P., A.h., and M.G. validation: O.K., J.t., S.v., and M.G. data curation: O.K., t.K., J.t., A.M., and M.G. Software: t.K. and A.h. visualization: O.K., t.K., J.t., P.P., and M.G. Resources: O.K., h.i., S.v., J.l.G., A.M., S.h., M.G., and J.R. Funding acquisition: J.t., S.h., O.K., J.l.G., and A.h. Supervision: J.t., O.K., J.l.G., K.S.l., t.K., S.h., and S.v. Project Administration: J.t., O.K., and S.v. Writing—original draft: O.K., J.t., P.P., S.v., M.G., and J.R. Writing—review and editing: J.t., O.K., t.K., S.h., K.S.l., J.l.G., A.M., S.v., h.i., B.S., and J.R. Competing interests: the authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper, the Supplementary Materials, or data repositories. PiSA data have been deposited to the ProteomeXchange consortium via the PRide partner repository with the dataset identifier PXd037155 (www.ebi.ac.uk/pride/archive/projects/PXd037155). scRnA-seq data have been deposited to Arrayexpress with the dataset identifier e-MtAB-13427 (www.ebi. ac.uk/biostudies/Arrayexpress/studies/e-MtAB-13427). Microarray data have been deposited to Gene expression Omnibus with identifier GSe294689 (www.ncbi.nlm.nih.gov/geo/query/ acc.cgi?acc=GSe294689). chiP-seq data have been deposited to enA with accession PRJeB88248 (www.ebi.ac.uk/ena/browser/view/PRJeB88248), cGe data with accession PRJeB88223 (www.ebi.ac.uk/ena/browser/view/PRJeB88223), and RnA-seq data with accession PRJeB88115 (www.ebi.ac.uk/ena/browser/view/PRJeB88115). this paper does not report original code.