PRMT5 promotes cancer cell migration and invasion through the E2F pathway

被引：35

作者：

Barczak, Wojciech ^{[1
]}

Jin, Li ^{[1
]}

Carr, Simon Mark ^{[1
]}

Munro, Shonagh ^{[2
]}

Ward, Samuel ^{[2
]}

Kanapin, Alexander ^{[3
]}

Samsonova, Anastasia ^{[3
]}

La Thangue, Nicholas B. ^{[1
]}

机构：

[1] Univ Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England

[2] Argonaut Therapeut Ltd, Magdalen Ctr, Oxford Sci Pk, Oxford OX4 4GA, England

[3] St Petersburg State Univ, Ctr Genome Bioinformat, St Petersburg 199034, Russia

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 07期

关键词：

GENE-EXPRESSION; ARGININE METHYLTRANSFERASE; PRB PATHWAY; CORTACTIN; PROTEIN; METASTASIS; OVEREXPRESSION; AMPLIFICATION; CARCINOMAS; ACTIVATION;

D O I：

10.1038/s41419-020-02771-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：13

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