Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer
Otto Kauko1,2,3, Mikko Turunen1,4, Päivi Pihlajamaa1
1Applied Tumor Genomics Program, University of Helsinki, Biomedicum, P.O. Box 63, Haartmaninkatu 8, Helsinki FIN-00014 University of Helsinki, Finland.
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.
Insights
Cancer genes target common pathways like translation and ribosome biogenesis to drive cell proliferation. Nucleolar and coiled-body phosphoprotein 1 is a key regulator identified across cancer types for tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer is driven by mutations in various genes, leading to common malignant phenotypes like uncontrolled cell growth.
- A hypothesis suggests that cancer genes converge on common targets to regulate essential cancer phenotypes.
Purpose of the Study:
- To identify common molecular mechanisms driving unrestricted cell proliferation, a hallmark of all tumors.
- To investigate shared targets regulated by major oncogenic pathways across different cancer types.
Main Methods:
- A multiomic approach was employed, integrating proteomic analysis of tumors and functional studies in cell cultures.
- Investigated transcriptional and posttranslational regulation of key protein nodes.
Main Results:
- Translation and ribosome biogenesis were identified as common targets of major oncogenic pathways across cancer types.
- Nucleolar and coiled-body phosphoprotein 1 (NCP1) was identified as a critical node for tumor cell proliferation.
- NCP1 exhibits convergent transcriptional and posttranslational regulation essential for tumor growth.
Conclusions:
- Lineage-specific oncogenic pathways converge on common targets to control cell growth.
- NCP1 represents a key downstream node that could be a therapeutic target for cancer treatment and chemoprevention.
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