A novel role for BRCA1 in regulating breast cancer cell spreading and motility

Coene, Elisabeth; Gadelha, Catarina; White, Nicholas; Malhas, Ashraf N.; Thomas, Benjamin; Shaw, Michael K.; Vaux, David J.

doi:10.1083/jcb.201004136

Cited by 56 publications

(63 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Work in Caenorhabditis elegans, Drosophila melanogaster (midlife crisis), and Danio rerio has also provided evidence for developmental defects (70)(71)(72)(73). The RING-Finger domain of this protein falls into the same family as the one contained in BRCA1, and there is evidence that BRCA1 regulates motility at the leading edge beyond its role of DNA repair in the nucleus (74).…”

Section: Regulators Of Adhesion and Motility Reveal Multiple Points Ofmentioning

confidence: 99%

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

Lampert

Kamprad

Edwards

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The model organism Dictyostelium discoideum has greatly facilitated our understanding of the signal transduction and cytoskeletal pathways that govern cell motility. Cell-substrate adhesion is downstream of many migratory and chemotaxis signaling events. Dictyostelium cells lacking the tumor suppressor PTEN show strongly impaired migratory activity and adhere strongly to their substrates. We reasoned that other regulators of migration could be obtained through a screen for overly adhesive mutants. A screen of restriction enzyme-mediated integration mutagenized cells yielded numerous mutants with the desired phenotypes, and the insertion sites in 18 of the strains were mapped. These regulators of adhesion and motility mutants have increased adhesion and decreased motility. Characterization of seven strains demonstrated decreased directed migration, flatness, increased filamentous actin-based protrusions, and increased signal transduction network activity. Many of the genes share homology to human genes and demonstrate the diverse array of cellular networks that function in adhesion and migration

show abstract

Section: Regulators Of Adhesion and Motility Reveal Multiple Points Ofmentioning

confidence: 99%

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

Lampert

Kamprad

Edwards

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Here, depletion of BRCA1 resulted in increased cell spreading and motility of single cells, as well as increased invasive behaviour of cells in wound healing assays in vitro (Coene et al, 2011). BRCA1 was also suggested to colocalise with radixin and moesin, therefore this interaction is not unique to ezrin (Coene et al, 2011). Could BRCA1 target ezrin in order to regulate its expression?…”

Section: Ezrinmentioning

confidence: 99%

“…Therefore, loss of BRCA1, as commonly seen in breast cancer cells, could result in an accumulation of ezrin that not only leads to its reported high expression in breast cancer cells but also an increased activity of specific signalling pathways that involve ezrin and regulate cell-cell contacts, cell adhesion and cell migration (Fig. 3) (Coene et al, 2011).…”

Section: Ezrinmentioning

confidence: 99%

“…The recent discovery of a new role for BRCA1, a well-established tumour suppressor gene in breast and ovarian cancer, in cell motility and invasion might shed light on the regulation of ezrin in breast cancer (Coene et al, 2011). Here, depletion of BRCA1 resulted in increased cell spreading and motility of single cells, as well as increased invasive behaviour of cells in wound healing assays in vitro (Coene et al, 2011). BRCA1 was also suggested to colocalise with radixin and moesin, therefore this interaction is not unique to ezrin (Coene et al, 2011).…”

Section: Ezrinmentioning

confidence: 99%

See 1 more Smart Citation

ERM proteins in cancer progression

Clucas

Valderrama

2014

Journal of Cell Science

223

152

View full text Add to dashboard Cite

Members of the ezrin–radixin–moesin (ERM) family of proteins are involved in multiple aspects of cell migration by acting both as crosslinkers between the membrane, receptors and the actin cytoskeleton, and as regulators of signalling molecules that are implicated in cell adhesion, cell polarity and migration. Increasing evidence suggests that the regulation of cell signalling and the cytoskeleton by ERM proteins is crucial during cancer progression. Thus, both their expression levels and subcellular localisation would affect tumour progression. High expression of ERM proteins has been shown in a variety of cancers. Mislocalisation of ERM proteins reduces the ability of cells to form cell–cell contacts and, therefore, promotes an invasive phenotype. Similarly, mislocalisation of ERM proteins impairs the formation of receptor complexes and alters the transmission of signals in response to growth factors, thereby facilitating tumour progression. In this Commentary, we address the structure, function and regulation of ERM proteins under normal physiological conditions as well as in cancer progression, with particular emphasis on cancers of epithelial origin, such as those from breast, lung and prostate. We also discuss any recent developments that have added to the understanding of the underlying molecular mechanisms and signalling pathways these proteins are involved in during cancer progression.

show abstract

“…5A). BRCA1 possesses E3 ubiquitin ligase activity (15), accumulates at leading edges in migrating cells (23), and is expressed during brain development (24), particularly in proliferative zones (Fig. 5B).…”

Section: Brca1 Is Expressed In Cholinergic Neurons: Implications For Mglmentioning

confidence: 99%

Nerve growth factor scales endocannabinoid signaling by regulating monoacylglycerol lipase turnover in developing cholinergic neurons

Keimpema

Tortoriello

Alpár

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Endocannabinoid, particularly 2-arachidonoyl glycerol (2-AG), signaling has recently emerged as a molecular determinant of neuronal migration and synapse formation during cortical development. However, the cell type specificity and molecular regulation of spatially and temporally confined morphogenic 2-AG signals remain unexplored. Here, we demonstrate that genetic and pharmacological manipulation of CB 1 cannabinoid receptors permanently alters cholinergic projection neuron identity and hippocampal innervation. We show that nerve growth factor (NGF), implicated in the morphogenesis and survival of cholinergic projection neurons, dose-dependently and coordinately regulates the molecular machinery for 2-AG signaling via tropomyosine kinase A receptors in vitro. In doing so, NGF limits the sorting of monoacylglycerol lipase (MGL), rate limiting 2-AG bioavailability, to proximal neurites, allowing cell-autonomous 2-AG signaling at CB 1 cannabinoid receptors to persist at atypical locations to induce superfluous neurite extension. We find that NGF controls MGL degradation in vitro and in vivo and identify the E3 ubiquitin ligase activity of breast cancer type 1 susceptibility protein (BRCA1) as a candidate facilitating MGL's elimination from motile neurite segments, including growth cones. BRCA1 inactivation by cisplatin or genetically can rescue and reposition MGL, arresting NGF-induced growth responses. These data indicate that NGF can orchestrate endocannabinoid signaling to promote cholinergic differentiation and implicate BRCA1 in determining neuronal morphology.axon guidance | basal forebrain | neurotrophin | protein stability | choline acetyltransferase C B 1 cannabinoid receptors (CB 1 Rs) are the targets of marijuana (Cannabis spp.)-derived phytocannabinoids and endocannabinoids, including 2-arachidonoyl glycerol (2-AG) (1). 2-AG liberated from postsynaptic neurons serves as a retrograde messenger to limit neurotransmitter release from many mature presynapses (1). However, 2-AG signaling also emerges as a molecular determinant of cortical development (2-4). Despite recent advances, the contribution of endocannabinoids (specifically 2-AG) to neuronal diversification and the development of synaptic connectivity in subcortical territories remains unknown. Cholinergic projection neurons within a continuum of magnocellular nuclei in the basal forebrain (5) are appealing candidates for developmental 2-AG actions considering their CB 1 R expression (1) and the endocannabinoid sensitivity of acetylcholine release in adulthood (6).Cholinergic afferents innervating the cerebral cortex are essential for learning and memory (5, 7). A favored approach to rescue cholinergic neurotransmission under disease conditions relies on neurotrophins to maintain the molecular identity, synaptic signaling, and survival of cholinergic neurons (8, 9). Nerve growth factor (NGF) appears particularly efficacious to promote the phenotypic differentiation and synaptic connectivity of postnatal cholinergic projection neurons (9, 10), as ill...

show abstract

A novel role for BRCA1 in regulating breast cancer cell spreading and motility

Abstract: BRCA1 interacts with ERM proteins at leading edges and focal adhesion sites and modulates motility via its ubiquitin ligase activity.

Cited by 56 publications

References 39 publications

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

ERM proteins in cancer progression

Nerve growth factor scales endocannabinoid signaling by regulating monoacylglycerol lipase turnover in developing cholinergic neurons

Contact Info

Product

Resources

About