Id2 Promotes Tumor Cell Migration and Invasion through Transcriptional Repression of Semaphorin 3F

Coma, Sílvia; Amin, Dhara N.; Shimizu, Akio; Lasorella, Anna; Iavarone, Antonio; Klagsbrun, Michael

doi:10.1158/0008-5472.can-09-3048

Cited by 79 publications

(59 citation statements)

References 40 publications

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“…Although accumulating evidence has demonstrated a correlation between semaphorin expression and glioma progression (Correa et al, 2001;Rieger et al, 2003;Rich et al, 2005), studies of the expression of plexins and the role of semaphorin-plexin interactions in gliomas remain scanty (Rieger et al, 2003;Bagci et al, 2009;Nasarre et al, 2009;Coma et al, 2010). Here, we show that plexin-B3 is expressed in human glioma cells, which upon activation by its ligand Sema5A inhibits cell motility, triggers cell collapse and promotes ramification of processes.…”

Section: Discussionmentioning

confidence: 73%

Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton

Law

Lee

2011

Oncogene

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Semaphorins are implicated in glioma progression, although little is known about the underlying mechanisms. We have reported plexin-B3 expression in human gliomas, which upon stimulation by Sema5A causes significant inhibition of cell migration and invasion. The concomitant inactivation of Rac1 is of mechanistic importance because forced expression of constitutively active Rac1 abolishes these inhibitory effects. Furthermore, Sema5A induces prominent cell collapse and ramification of processes reminiscent of astrocytic morphology, which temporally associate with extensive disassembly of actin stress fibers and disruption of focal adhesions, followed by accumulation of actin patches in protrusions. Mechanistically, Sema5A induces transient protein kinase C (PKC) phosphorylation of fascin-1, which can reduce its actin-binding/bundling activities and temporally parallels its translocation from cell body to extending processes. PKC inhibition or fascin-1 knockdown is sufficient to abrogate Sema5A-induced morphological differentiation, whereas the process is hastened by forced expression of fascin-1. Intriguingly, Sema5A induces re-expression of glial fibrillary acidic protein (GFAP), which when silenced restricts differentiation of glioma cells to bipolar instead of multipolar morphology. Therefore, we hypothesize complementary functions of fascin-1 and GFAP in the early and late phases of Sema5A-induced astrocytic differentiation of gliomas, respectively. In summary, Sema5A and plexin-B3 impede motility but promote differentiation of human gliomas. These effects are plausibly compromised in high-grade human astrocytomas in which Sema5A expression is markedly reduced, hence leading to infiltrative and anaplastic characteristics. This is evident by increased invasiveness of glioma cells when endogenous Sema5A is silenced. Therefore, Sema5A and plexin-B3 represent potential novel targets in counteracting glioma progression.

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Section: Discussionmentioning

confidence: 73%

Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton

Law

Lee

2011

Oncogene

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“…SEMA3A can dramatically inhibit the proliferation and reduce both the migratory and invasive behavior of breast tumor cells (9,10). SEMA3F is the most studied semaphorin and acts as a tumor suppressor gene by reducing angiogenesis and metastasis, probably through the inhibition of integrin mediated adhesion and VEGF expression (19,20,(34)(35)(36)(37)(38). SEMA3B, like SEMA3F and SEMA3A, is also described as a tumor suppressor gene (5,15).…”

Section: Discussionmentioning

confidence: 99%

Effects of SEMA3G on migration and invasion of glioma cells

Zhou

et al. 2012

Oncol Rep

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Abstract. Glioblastoma multiforme is the most aggressive type of brain tumor with a strong ability to invade and migrate into surrounding normal brain tissues, leading to high tumor recurrence and mortality. Most of class-3 semaphorins, especially SEMA3A, SEMA3B and SEMA3F, have been reported to have strong tumor inhibition ability, but the role of SEMA3G in tumor biology is largely unknown. We report here that SEMA3G possesses anti-migration and anti-invasion ability. To determine the potential effects of SEMA3G on migratory and invasive ability, we generated stable SEMA3G expression U251MG cells. We found that stably overexpressed SEMA3G inhibited the migratory and invasive behavior of U251MG cells. In addition, treatment with SEMA3G conditioned media also decreased the migratory and invasive ability of parental U251MG cells. Furthermore, SEMA3G also inhibited the activity of MMP2, an index of tumor invasion ability. Thus, our results suggest that SEMA3G inhibited tumor cell migration and invasion, which may be obtained through cell autonomous or paracrine mechanisms, and SEMA3G is a potential target for antitumor migration and invasion.

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“…Inhibitor of DNA binding 2 (ID2), an angiogenic gene promoting endothelial cell growth and migration (2,7,25), was upregulated by the frequency step-up. Importantly, ID2 was one of the three genes that were also upregulated by the magnitude step-up, suggest- Fig.…”

Section: Resultsmentioning

confidence: 99%

Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

Zhang

Friedman

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang J, Friedman MH. Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency. Am J Physiol Heart Circ Physiol 305: H894 -H902, 2013. First published July 12, 2013 doi:10.1152/ajpheart.00174.2013.-Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study (41), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 Ϯ 15 dyn/cm 2 at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay. endothelial permeability; gene expression; adaptation; shear stress; frequency THE ENDOTHELIAL CELLS lining blood vessels are constantly exposed to shear stress, the friction force from blood flow, and their function is tightly regulated by this external mechanical stimulus. For decades, researchers have studied how shear stress profiles regulate endothelial permeability and gene expression and, consequently, affect the pathogenesis of atherosclerosis (4, 5, 9). Prolonged unidirectional shear stress is generally considered to be atheroprotective, since it leads to a better endothelial barrier function (6,17,19) and an antiinflammatory endothelial phenotype (11). On the other hand, "disturbed" shear stress, a term that is still poorly defined, promotes a proinflammatory phenotype and increased permeability (9, 11). Our understanding of endothelial mechanobiology has been advanced by studies that have isolated the endothelial response to different parameters of the shear stress profile, including shear stress magnitude (13), frequency (15), temporal (1) and spatial (20) gradient, and...

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Id2 Promotes Tumor Cell Migration and Invasion through Transcriptional Repression of Semaphorin 3F

Cited by 79 publications

References 40 publications

Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton

Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton

Effects of SEMA3G on migration and invasion of glioma cells

Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

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