Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells

Barbetti, Valentina; Morandi, Andrea; Tusa, Ignazia; Digiacomo, Graziana; Riverso, Maria; Marzi, Ilaria; Cipolleschi, Maria Grazia; Bessi, Silvia; Giannini, A. James; Leo, Angelo Di; Sbarba, Persio Dello; Rovida, Elisabetta

doi:10.1038/onc.2013.542

Cited by 26 publications

(26 citation statements)

References 48 publications

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“…2 B ). Treatment with siCSF1R determined a decrease in CSF1R expression, in keeping with previous reports (25, 26). CSF1R silencing inhibited PGE2‐induced ERK1/2 phosphorylation with respect to control, nontargeting siRNA (Fig.…”

Section: Resultssupporting

confidence: 92%

Prostaglandin E2 transactivates the colony‐stimulating factor‐1 receptor and synergizes with colony‐stimulating factor‐1 in the induction of macrophage migrationviathe mitogen‐activated protein kinase ERK1/2

et al. 2015

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Prostaglandin E2 (PGE2), a key mediator of immunity, inflammation, and cancer, acts through 4 G-protein-coupled E-prostanoid receptors (EPs 1-4). Crosstalk between EPs and receptor tyrosine kinases also occurs. Colony-stimulating factor-1 receptor (CSF-1R) is an RTK that sustains the survival, proliferation, and motility of monocytes/macrophages, which are an essential component of innate immunity and cancer development. The aim of this study was to investigate on a possible crosstalk between EP and CSF-1R. In BAC1.2F5 and RAW264.7 murine macrophages, CSF-1 (EC 50 = 18.1 and 10.2 ng/ml, respectively) and PGE2 (EC 50 = 1.5 and 5.5 nM, respectively) promoted migration. PGE2 induced rapid CSF-1R phosphorylation that was dependent on Src family kinases (SFKs). CSF-1R inhibition reduced PGE2-elicited ERK1/2 phosphorylation and macrophage migration, indicating that CSF-1R plays a role in PGE2-mediated immunoregulation. EP4 appeared responsible for functional PGE2/CSF-1R crosstalk. Furthermore, PGE2 synergized with CSF-1 in inducing ERK1/2 phosphorylation and macrophage migration. ERK1/2 inhibition completely blocked migration induced by the combination CSF-1/PGE2. CSF-1/ PGE2 functional interaction with respect to migration also occurred in bone marrow-derived murine macrophages (EC 50 CSF-1, 6.7 ng/ml; EC 50 PGE2, 16.7 nM). These results indicated that PGE2 transactivates CSF-1R and synergizes with its signaling at ERK1/2 level in promoting macrophage migration.-Digiacomo, G., Ziche, M., Sbarba, P. D., Donnini, S., Rovida, E. Prostaglandin E2 transactivates the colony-stimulating factor-1 receptor and synergizes with colony-stimulating factor-1 in the induction of macrophage migration via the mitogen-activated protein kinase ERK1/21. FASEB J. 29, 2545-2554 (2015). www.fasebj.org

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Section: Resultssupporting

confidence: 92%

Prostaglandin E2 transactivates the colony‐stimulating factor‐1 receptor and synergizes with colony‐stimulating factor‐1 in the induction of macrophage migrationviathe mitogen‐activated protein kinase ERK1/2

et al. 2015

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“…Recently, Barbetti et al [238] reported nuclear translocation of the CSF-1R holoreceptor and its functions in breast cancer. They showed that nuclear CSF-1R was present only in breast cancer cells but not in fibroblasts or macrophages.…”

Section: Pdgfr Familymentioning

confidence: 99%

Proteolytic cleavage, trafficking, and functions of nuclear receptor tyrosine kinases

Chen

Hung

2015

The FEBS Journal

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Over three quarters of receptor tyrosine kinase (RTK) families are reported to have intracellular localization in response to environmental stimuli. Internalized RTK can bind to non-canonical substrates and affect various cellular processes. Many of the intracellular RTKs exist as fragmented forms that are generated by γ-secretase cleavage of the full-length receptor, shedding, alternative splicing, or alternative translation initiation. Soluble RTK fragments are stabilized and intracellularly transported into subcellular compartments, such as the nucleus, by binding to chaperon or transcription factors while membrane-bound RTKs (full-length or truncated) are transported from the plasma membrane to the endoplasmic reticulum (ER) through the well-established Rab- or clathrin adaptor protein (AP)-coated vesicle retrograde trafficking pathway. Subsequent nuclear transport of membrane-bound RTK can occur via two pathways, INFS and INTERNET, with the former characterized by the release of receptors from ER into the cytosol and the latter by the release of membrane-bound transport from the ER into the nucleoplasm through the inner nuclear membrane. While most non-canonical intracellular RTK signaling is related to transcriptional regulation, there may be other functions that have yet to be discovered. In this review, we summarize the proteolytic processing, intracellular trafficking, and nuclear functions of RTKs and discuss how they promote cancer progression and their clinical implications.

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“…Immunofluorescence was performed as previously described. 41 Briefly, after fixation with 4% paraformaldehyde and permeabilization cells were incubated (overnight, 4 C) in PBS-1%…”

Section: Immunofluorescencementioning

confidence: 99%

Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway

Digiacomo

Tusa

Bacci

et al. 2016

Cell Adhesion & Migration

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Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and b1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.

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Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells

Cited by 26 publications

References 48 publications

Prostaglandin E2 transactivates the colony‐stimulating factor‐1 receptor and synergizes with colony‐stimulating factor‐1 in the induction of macrophage migrationviathe mitogen‐activated protein kinase ERK1/2

Prostaglandin E2 transactivates the colony‐stimulating factor‐1 receptor and synergizes with colony‐stimulating factor‐1 in the induction of macrophage migrationviathe mitogen‐activated protein kinase ERK1/2

Proteolytic cleavage, trafficking, and functions of nuclear receptor tyrosine kinases

Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway

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