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Kauko O, Turunen M, Pihlajamaa P, Häkkinen A, Queiroz RML, Pääkkönen M, Ventelä S, Gaetani M, Lundström SL, Murgia A, Sahu B, Routila J, Wei GH, Irjala H, Griffin JL, Lilley KS, Kivioja T, Hautaniemi S, Taipale J
Sci Adv 11 (34) eadt1798 [2025-08-22; online 2025-08-20]
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.
Chemical Proteomics [Collaborative]
PubMed 40834066
DOI 10.1126/sciadv.adt1798
Crossref 10.1126/sciadv.adt1798