Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer
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.
Authors
- Teemu Kivioja (ORCID: https://orcid.org/0000-0002-7732-2177)
- Heikki Irjala (ORCID: https://orcid.org/0000-0003-3054-4677)
- Kathryn S. Lilley (ORCID: https://orcid.org/0000-0003-0594-6543)
- Susanna L. Lundström (ORCID: https://orcid.org/0000-0003-2363-4287)
- Jussi Taipale (ORCID: https://orcid.org/0000-0003-4204-0951)
- Mikko Turunen (ORCID: https://orcid.org/0000-0001-5134-1559)
- Sampsa Hautaniemi (ORCID: https://orcid.org/0000-0002-7749-2694)
- Antti Häkkinen (ORCID: https://orcid.org/0000-0002-8081-1588)
- Sami Ventelä (ORCID: https://orcid.org/0000-0001-6672-6662)
- Johannes Routila (ORCID: https://orcid.org/0000-0001-5385-7065)
- Massimiliano Gaetani (ORCID: https://orcid.org/0000-0001-5610-0797)
- Rayner M. L. Queiroz (ORCID: https://orcid.org/0000-0001-9866-4056)
- Mirva Pääkkönen (ORCID: https://orcid.org/0000-0002-3184-3938)
- Antonio Murgia
- Päivi Pihlajamaa (ORCID: https://orcid.org/0000-0001-9725-6907)
- Biswajyoti Sahu (ORCID: https://orcid.org/0000-0001-6576-5440)
- Otto Kauko (ORCID: https://orcid.org/0000-0001-8948-9452)
- Julian Leether Griffin (ORCID: https://orcid.org/0000-0003-1336-7744)
- Gong-Hong Wei
Institutions
- Åbo Akademi University (FI)
- University of Helsinki (FI)
- University of Turku (FI)
- University of Oslo (NO)
- University of Aberdeen (GB)
- University of Cambridge (GB)
- Columbia University Irving Medical Center (US)
- Science for Life Laboratory (SE)
- Helsinki Institute of Physics (FI)
- Turku University Hospital (FI)
- Karolinska Institutet (SE)
- University of Oulu (FI)
Publication Details
- Journal
- Science Advances
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1126/sciadv.adt1798
- Primary Topic
- Ubiquitin and proteasome pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00