JNK signaling pathway is required for bFGF-mediated surface cadherin downregulation on HUVEC

Wu, Jun; Yan, Horng-Chin; Chen, Wei-Teing; Chen, Wei-Hwa; Wang, Chia-Jen; Chi, Ying-Chih; Kao, Woei‐Yau

doi:10.1016/j.yexcr.2007.10.002

Cited by 25 publications

(24 citation statements)

References 53 publications

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“…Since the expression of furin proteases was shown to be developmentally regulated in different tissues (Kayo et al, 1996Konda et al, 1997;Nakayama, 1997), the increased activity of such enzyme(s) could regulate the ratio of ProN/N-cad during development. Another possible regulatory mechanism could be increased internalization (Wu et al, 2008) as we also show that, as the CNS develops, ProN is found associated with plasma membrane tubular invaginations (Immuno EM; Fig. 8) previously described as related to endocytic phenomena (Smith et al, 2008;Dittman and Ryan, 2009).…”

Section: Discussionsupporting

confidence: 67%

N-Cadherin Prodomain Processing Regulates Synaptogenesis

Reinés

Bernier²,

McAdam³

et al. 2012

J. Neurosci.

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Classical cadherins, which are adhesion molecules functioning at the CNS synapse, are synthesized as adhesively inactive precursor proteins in the endoplasmic reticulum (ER). Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respectively, activates their adhesive properties. Here, we provide the first evidence for sorting of nonadhesive precursor N-cadherin (ProN) to the neuronal surface, where it coexists with adhesively competent mature N-cadherin (N-cad), generating a spectrum of adhesive strengths. In cultured hippocampal neurons, a high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The synapse number can be rescued to normality by depleting surface ProN levels through prodomain cleavage by an exogenous protease. Finally, prodomain processing is developmentally regulated in the rat hippocampus. We conclude that it is the ProN/N-cad ratio and not mature N-cad alone that is critical for regulation of adhesion during synaptogenesis.

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Section: Discussionsupporting

confidence: 67%

N-Cadherin Prodomain Processing Regulates Synaptogenesis

Reinés

Bernier²,

McAdam³

et al. 2012

J. Neurosci.

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“…In contrast, previous in vitro studies and the gene expression profiling of advanced ovarian cancer suggest that FGF2 acts as an autocrine growth factor for ovarian cancer cell proliferation [9]–[11] and invasion [12]. Moreover, FGF2 regulates the expression of additional genes implicated in angiogenesis or metastasis, including metalloproteinases [13], vascular endothelial growth factor [14], and E-cadherin [13], [15], [16].…”

Section: Introductionmentioning

confidence: 87%

Fibroblast Growth Factor 2 Induces E-Cadherin Down-Regulation via PI3K/Akt/mTOR and MAPK/ERK Signaling in Ovarian Cancer Cells

Lau

Leung

2013

PLoS ONE

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Fibroblast growth factor 2 (FGF2) is produced by ovarian cancer cells and it has been suggested to play an important role in tumor progression. In this study, we report that FGF2 treatment down-regulated E-cadherin by up-regulating its transcriptional repressors, Slug and ZEB1, in human ovarian cancer cells. The pharmacological inhibition of phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR), and MEK suggests that both PI3K/Akt/mTOR and MAPK/ERK signaling are required for FGF2-induced E-cadherin down-regulation. Moreover, FGF2 up-regulated Slug and ZEB1 expression via the PI3K/Akt/mTOR and MAPK/ERK signaling pathways, respectively. Finally, FGF2-induced cell invasion was abolished by the inhibition of the PI3K/Akt/mTOR and MAPK/ERK pathways, and the forced expression of E-cadherin diminished the intrinsic invasiveness of ovarian cancer cells as well as the FGF2-induced cell invasion. This study demonstrates a novel mechanism in which FGF2 down-regulates E-cadherin expression through the activation of PI3K/Akt/mTOR and MAPK/ERK signaling, and the up-regulation of Slug and ZEB1 in human ovarian cancer cells.

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“…33 In human umbilical vein endothelial cells, bFGF promotes proliferation and migration via JNK whereas p38 MAPK induces endothelial cell differentiation. 40 Treatment with bFGF activates ERK and JNK in neuroblastoma JK-GMS cells, thus resulting in growth inhibition, neuronal differentiation and apoptosis. 41 The current results clearly showed that bFGF activated JNK1 but not JNK2 ⁄3, and JNK1 plays a role in the proliferation stimulated by bFGF.…”

Section: Discussionmentioning

confidence: 99%