Class 3 semaphorins in cardiovascular development

Valdembri, Donatella; Regano, Donatella; Maione, Federica; Giraudo, Enrico; Serini, Guido

doi:10.1080/19336918.2016.1212805

Cited by 47 publications

(51 citation statements)

References 115 publications

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“…NRP1 and NRP2 are co-receptors that bind to and interact with a variety of growth factors (17,18). NRP1 is a transmembrane glycoprotein that binds to various extracellular ligands, including class III/IV semaphorins (19), certain isoforms of vascular endothelial growth factor (VEGF) (20), TGF-β1 (15), and platelet-derived growth factor (PDGF) (21). A previous study by the authors demonstrated that the expression of NRP1 was high in NSCLC tissues and was associated with a poorer survival of patients (22).…”

Section: Neuropilin 1 Modulates Tgf-β1-induced Epithelial-mesenchymalmentioning

confidence: 99%

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Ding

et al. 2019

Int J Oncol

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Previously, the authors reported that neuropilin-1 (NRP1) was significantly increased and acted as a vital promoter in the metastasis of non-small cell lung cancer (NSCLC). However, the regulatory mechanism of NRP1 in NSCLC cell migration and invasion remained unclear. The present study aimed to explore the regulatory mechanism of NRP1 in the transforming growth factor-β (TGF-β) 1-induced migration and invasion of NSCLC cells. The expression level of NRP1 was determined by RT-qPCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine the cell migration. Lentivirus-mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF-β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanisms. The results demonstrated that the expression of NRP1 was increased in metastatic NSCLC tissues. NRP1 promoted NSCLC metastasis in vitro and in vivo. The Transwell assays, wound healing assays and western blot analysis revealed that the knockdown of NRP1 significantly inhibited TGF-β1-mediated EMT and migratory and invasive capabilities of NSCLC. Furthermore, the overexpression of NRP1 weakened the inhibitory effect of SIS3 on the NSCLC migration and invasion. Co-IP assay revealed that NRP1 interacted with TGFβRII to induce EMT. On the whole, the findings of this study demonstrated that NRP1 was overexpressed in metastatic NSCLC tissues. NRP1 could contributes to TGF-β1-induced EMT and metastasis in NSCLC by binding with TGFβRII.

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Section: Neuropilin 1 Modulates Tgf-β1-induced Epithelial-mesenchymalmentioning

confidence: 99%

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Ding

et al. 2019

Int J Oncol

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“…Additionally, binding of SEMA3C to NRPs activates PLXN co-receptors, stimulating downstream signal pathways. Among the nine PLXNs, it is reported that SEMA3C mainly activates PLXNA2, PLXNB1, or PLXND1 [13][14][15]. When cell viability was measured at 72 h after knockdown of each PLXN, PLXNB1 deficiency suppressed the cell viability most strongly (online suppl.…”

Section: Sema3c Sustained the Growth Of Pkd Epithelialmentioning

confidence: 96%

Semaphorin-3C Is Upregulated in Polycystic Kidney Epithelial Cells and Inhibits Angiogenesis of Glomerular Endothelial Cells

Kim

et al. 2020

Am J Nephrol

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Background: Polycystic kidney disease (PKD) is a hereditary disease characterized by cyst formation in the kidneys bilaterally. It has been observed that semaphorin-3C (SEMA3C) is overexpressed in polycystic kidney epithelial cells. It is hypothesized that upregulated SEMA3C would contribute to survival of polycystic kidney epithelial cells. Furthermore, as the kidney is a highly vascularized organ, the secreted SEMA3C from PKD epithelial cells will affect glomerular endothelial cells (GECs) in a paracrine manner. Methods: To evaluate the effect of SEMA3C on renal cells, siSEMA3C-treated PKD epithelial cells were used for further analysis, and GECs were exposed to recombinant SEMA3C (rSEMA3C). Also, co-culture and treatment of conditioned media were employed to confirm whether PKD epithelial cells could influence on GECs via SEMA3C secretion. Results: SEMA3C knockdown reduced proliferation of PKD epithelial cells. In case of GECs, exposure to rSEMA3C decreased angiogenesis, which resulted from suppressed migratory ability not cell proliferation. Conclusions: This study indicates that SEMA3C is the aggravating factor in PKD. Thus, it is proposed that targeting SEMA3C can be effective to mitigate PKD.

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“…For instance, the Rap1-GTP-interacting adapter molecule (RIAM) can either promote, through talin, the conformational activation of integrin adhesion receptors at the leading edge of migrating cells (Lagarrigue et al, 2016) or favor, via the mitogen-activated protein kinase kinase MEK, the disassembly of centrally located focal adhesions (FAs) (Coló et al, 2012). Furthermore, major repulsive guidance cues such as secreted class 3 Semaphorins control blood vessel patterning (Valdembri et al, 2016;Wälchli et al, 2015) through the cytosolic GTPase activating protein domain of Plexin receptors ) that negatively regulates Rap1 signaling (Gioelli et al, 2018;Wang et al, 2012). On the contrary, GPCRs promote Rap1 GTP loading via different pathways, the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP (EPAC) guanine nucleotide exchange factor cascade being a foremost one (Algire, 1943;Chang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

Camillo

Facchinello

Villari

et al. 2020

Preprint

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Dynamic modulation of endothelial cell (EC) adhesion to extracellular matrix (ECM) in response to mechanostimuli is essential for blood vessel patterning and functioning. Yet, the molecular mechanisms involved in this biological process are far to be completely deciphered. Here, we identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of vascular morphogenesis and endothelial barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM adhesions, signals through cAMP/Rap1, and, via its fibronectin-leucine-rich transmembrane (FLRT)-binding domain, negatively regulates ECM-elicited haptotaxis. ECs also express endogenous FLRT2 ligand that promotes cAMP/Rap1 signaling and hinders haptotaxis in a LPHN2-dependent manner. Vascular ECs of lphn2a knock-out zebrafish embryos become abnormally stretched, display a hyperactive Hippo mechanosensing pathway, and lack proper intercellular junctions. Indeed, intravascularly injected cancer cells extravasate more easily in lphn2a null animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.

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Class 3 semaphorins in cardiovascular development

Cited by 47 publications

References 115 publications

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Semaphorin-3C Is Upregulated in Polycystic Kidney Epithelial Cells and Inhibits Angiogenesis of Glomerular Endothelial Cells

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

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