PRMT5 promotes cancer cell migration and invasion through the E2F pathway

The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the f...

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Bibliographic Details
Published in:Cell death & disease 2020-07, Vol.11 (7), p.572-572, Article 572
Main Authors: Barczak, Wojciech, Jin, Li, Carr, Simon Mark, Munro, Shonagh, Ward, Samuel, Kanapin, Alexander, Samsonova, Anastasia, La Thangue, Nicholas B.
Format: Article
Language:English
Subjects:
631/67/1504/1885/1393
631/80/79/2027
Antibodies
Arginine
Biochemistry
Biomedical and Life Sciences
Cancer
Cell adhesion & migration
Cell Biology
Cell Culture
Cell cycle
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cortactin - genetics
Cortactin - metabolism
Down-Regulation - genetics
E2F1 protein
E2F1 Transcription Factor - genetics
E2F1 Transcription Factor - metabolism
Focal Adhesions - metabolism
Gene Expression Regulation, Neoplastic
Genome, Human
Genomes
Humans
Immunology
Life Sciences
Neoplasm Invasiveness
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Phenotypes
Protein-Arginine N-Methyltransferases - antagonists & inhibitors
Protein-Arginine N-Methyltransferases - genetics
Protein-Arginine N-Methyltransferases - metabolism
Signal Transduction - genetics
Tumors
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Summary:The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-02771-9