EphrinB1 Interacts with CNK1 and Promotes Cell Migration through c-Jun N-terminal Kinase (JNK) Activation

Cho, Hee Jun; Hwang, Yoo-Seok; Mood, Kathleen; Ji, Yon Ju; Morrison, Deborah K.; Daar, Ira

doi:10.1074/jbc.m114.558809

Cited by 25 publications

(30 citation statements)

References 53 publications

(30 reference statements)

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“…Previous studies have demonstrated the importance of the c‐Jun N‐terminal kinase (JNK) pathway in the regulation of cell migration . Based on these studies, we hypothesized that JNK is also involved in bFGF‐induced melanocyte migration.…”

Section: Resultsmentioning

confidence: 95%

Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt‐Rac1‐FAK‐JNK and ERK signaling pathways

et al. 2016

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Vitiligo is a depigmentation disorder characterized by loss of functional melanocytes of the skin epidermis. The pathogenesis of vitiligo remains elusive. The purpose of this study is to investigate the effects of basic fibroblast growth factor (bFGF) on melanocyte migration, including its biochemical mechanism using transwell assay in vitro. We found that melanocyte treated with bFGF showed a significant increase in migration and cytoskeletal rearrangement. These changes were associated with increased activation of PI3K/Akt, Rac1, FAK, JNK, and ERK. Likewise, reduction of PI3K/Akt, Rac1, FAK, JNK, and ERK activity using selective inhibitors or siRNA was associated with impediment of bFGF-induced melanocyte migration. In addition, activity of Rac1, FAK, and JNK was reduced in cells in which PI3K/Akt was inhibited, activity of FAK and JNK was reduced in cells in which the Rac1 was inhibited, and activity of JNK was reduced in cells in which the FAK was inhibited. Collectively, these data demonstrate that bFGF facilitated melanocyte migration via PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways. V C 2016 IUBMB Life, 68(9): [735][736][737][738][739][740][741][742][743][744][745][746][747] 2016

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Section: Resultsmentioning

confidence: 95%

Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt‐Rac1‐FAK‐JNK and ERK signaling pathways

et al. 2016

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“…These include, for example, connecting Ephrin B stimulation via small GTPases to c-Jun N-terminal kinase (JNK) activation resulting in net cancer cell migration, or promoting cancer cell proliferation through the Akt-FoxO signalling axis [19, 20]. Recent studies using phosphomimetic mutants of CNKSR1 have identified phosphorylation sites in the scaffold critical for nuclear translocation and activation of MAPK pathway genes [21].…”

Section: Introductionmentioning

confidence: 99%

Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer

et al. 2017

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BackgroundDespite the near universal occurrence of activating codon 12 KRAS somatic variants in pancreatic cancer, there is considerable heterogeneity in the molecular make-up, MAPK/ERK pathway activation states, and clinical outcome in this disease. We analyzed the expression levels of CNKSR1, a scaffold that influences MAPK/ERK pathway activity, in clinical pancreas cancer specimens and their impact on survival of patients with pancreatic cancer.MethodsImmunohistochemical staining for CNKSR1 expression was performed on 120 specimens from three independent pancreatic cancer tissue registries, phospho-ERK levels were measured in 86 samples. Expression was divided into CNKSR1 low and CNKSR1 high and correlated with clinicopathological variables including overall survival using multivariate Cox proportional hazard ratio models.ResultsCNKSR1 expression was increased in tumors compared to matched normal uninvolved resection specimens (p = 0.004). 28.3% (34/120) of patient specimens stained as CNKSR1 low compared to 71.7% (86/120) of specimens which stained as CNKSR1 high. High CNKSR1 expression was more prevalent in low grade tumors (p = 0.04). In multivariate analysis, low CNKSR1 expression status was independently correlated with decreased overall survival (HR = 2.146; 95% CI 1.34 to 3.43). When stratifying primary, non-metastatic tumor biopsies by CNKSR1 expression, resection was associated with improved survival in patients with high CNKSR1 expression (p < 0.0001) but not low CNKSR1 expression (p = 0.3666). Pancreatic tumors with nuclear in addition to cytoplasmic CNKSR1 staining (32/107) showed increased nuclear phospho-ERK expression compared to tumor with cytoplasmic CNKSR1 staining only (p = 0.017).ConclusionCNKSR1 expression is increased in pancreatic tissue specimens and was found to be an independent prognostic marker of overall survival. CNKSR1 may help to identify patient subgroups with unfavorable tumor biology in order to improve risk stratification and treatment selection. Cellular distribution of CNKSR1 was correlated with nuclear pERK expression.

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“…Axon guidance recruits specific paths and defines their termination zones and synaptic partners (Cho et al 2014; Lim et al 2008), and is required for the development, maintenance, and plasticity of neural circuits (Curinga and Smith 2008). Axon guidance is relevant in adult life in response to injury.…”

Section: Discussionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques

Simon

Song

Stouwe

et al. 2015

J Neuroimmune Pharmacol

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Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

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EphrinB1 Interacts with CNK1 and Promotes Cell Migration through c-Jun N-terminal Kinase (JNK) Activation

Cited by 25 publications

References 53 publications

Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt‐Rac1‐FAK‐JNK and ERK signaling pathways

Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt‐Rac1‐FAK‐JNK and ERK signaling pathways

Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques

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