scholarly journals PRMT5 promotes cancer cell migration and invasion through the E2F pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wojciech Barczak ◽  
Li Jin ◽  
Simon Mark Carr ◽  
Shonagh Munro ◽  
Samuel Ward ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Cell Biology ◽  
Arginine Methylation ◽  
Migration And Invasion ◽  
Genome Wide ◽  
A Genome ◽  
Important Pathway ◽  
Major Target

Abstract 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.

scholarly journals Expression and Functional Role of CCR9 in Prostate Cancer Cell Migration and Invasion

2004 ◽  
Vol 10 (24) ◽  
pp. 8743-8750 ◽  
Author(s):  
Shailesh Singh ◽  
Udai P. Singh ◽  
Jonathan K. Stiles ◽  
William E. Grizzle ◽  
James W. Lillard
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Functional Role ◽  
Prostate Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion

scholarly journals The C-Terminus Tail Regulates ERK3 Kinase Activity and Its Ability in Promoting Cancer Cell Migration and Invasion

2020 ◽  
Vol 21 (11) ◽  
pp. 4044 ◽  
Author(s):  
Lobna Elkhadragy ◽  
Hadel Alsaran ◽  
Weiwen Long
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
C Terminus

Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family. It harbors a kinase domain in the N-terminus and a long C-terminus extension. The C-terminus extension comprises a conserved in ERK3 and ERK4 (C34) region and a unique C-terminus tail, which was shown to be required for the interaction of ERK3 with the cytoskeletal protein septin 7. Recent studies have elucidated the role of ERK3 signaling in promoting the motility and invasiveness of cancer cells. However, little is known about the intramolecular regulation of the enzymatic activity and cellular functions of ERK3. In this study, we investigated the role of the elongated C-terminus extension in regulating ERK3 kinase activity and its ability to promote cancer cell migration and invasion. Our study revealed that the deletion of the C-terminus tail greatly diminishes the ability of ERK3 to promote the migration and invasion of lung cancer cells. We identified two molecular mechanisms underlying this effect. Firstly, the deletion of the C-terminus tail decreases the kinase activity of ERK3 towards substrates, including the oncogenic protein steroid receptor co-activator 3 (SRC-3), an important downstream target for ERK3 signaling in cancer. Secondly, in line with the previous finding that the C-terminus tail mediates the interaction of ERK3 with septin 7, we found that the depletion of septin 7 abolished the ability of ERK3 to promote migration, indicating that septin 7 acts as a downstream effector for ERK3-induced cancer cell migration. Taken together, the findings of this study advance our understanding of the molecular regulation of ERK3 signaling by unraveling the role of the C-terminus tail in regulating ERK3 kinase activity and functions in cancer cells. These findings provide useful insights for the development of therapeutic agents targeting ERK3 signaling in cancer.

scholarly journals The Golgi in Cell Migration: Regulation by Signal Transduction and Its Implications for Cancer Cell Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Valentina Millarte ◽  
Hesso Farhan
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Posttranslational Modification ◽  
Metastatic Cancer ◽  
Migration And Invasion ◽  
Polarized Secretion ◽  
Cell Metastasis ◽  
Directional Cell Migration

Migration and invasion are fundamental features of metastatic cancer cells. The Golgi apparatus, an organelle involved in posttranslational modification and sorting of proteins, is widely accepted to regulate directional cell migration. In addition, mounting evidence suggests that the Golgi is a hub for different signaling pathways. In this paper we will give an overview on how polarized secretion and microtubule nucleation at the Golgi regulate directional cell migration. We will review different signaling pathways that signal to and from the Golgi. Finally, we will discuss how these signaling pathways regulate the role of the Golgi in cell migration and invasion. We propose that by identifying regulators of the Golgi, we might be able to uncover unappreciated modulators of cell migration. Uncovering the regulatory network that orchestrates cell migration is of fundamental importance for the development of new therapeutic strategies against cancer cell metastasis.

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