Y-Box Protein 1 Stimulates Mesangial Cell Proliferation via Activation of ERK1/2

Feng, Qi Sheng; Huang, Songming; Zhang, Aihua; Chen, Qiuxia; Guo, Xirong; Chen, Ronghua; Yang, Tianxin

doi:10.1159/000228079

Cited by 17 publications

(16 citation statements)

References 69 publications

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“…Therefore, the present study may have revealed the undiscovered function of YB-1 as a proteasomal regulator. The specificity between YB-1 and ERK2, and YB-1 and Raf-1 can be supported by the previous findings that ERK2 phosphorylated YB-1 (11) and Raf-1 regulation by YB-1 (38). Furthermore, considering the distinct role of Raf and ERK isoforms, the selective binding of YB-1 to Raf-1 and ERK2, but not to A-Raf, B-Raf and ERK1, makes us curious on this specificity.…”

Section: Discussionsupporting

confidence: 70%

“…In addition, Lee and colleagues indicated that YB-1 knockdown decreased STAT3 phosphorylation at Ser727 in breast cancer, accompanied by decreases of ERK and mTOR phosphorylation (16), although a mechanical investigation was not conducted. Furthermore, Feng and colleagues reported that YB-1 induced rat mesangial cell proliferation through ERK1/2 signaling, and ERK regulated YB-1 expression under inflammatory conditions (38). For the first time, the present study elucidated the mechanism of MEK/ERK/RSK regulation by YB-1.…”

Section: Discussionmentioning

confidence: 49%

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Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box–Binding Protein-1 Promotes Prostate Cancer Progression

Imada

Shiota

Kohashi

et al. 2013

Clinical Cancer Research

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Purpose: Y-box-binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, we aimed to examine the interaction between YB-1 and the MAPK pathway in prostate cancer.Experimental Design: Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.Results: EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527-20.508; P < 0.0001].Conclusion: We revealed the functional relationship between YB-1 and MAPK signaling and its biochemical relevance to the progression of prostate cancer. In addition, ERK2 expression was an independent prognostic factor. These findings suggest that both the ERK pathway and YB-1 may be promising molecular targets for prostate cancer diagnosis and therapeutics.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 49%

Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box–Binding Protein-1 Promotes Prostate Cancer Progression

Imada

Shiota

Kohashi

et al. 2013

Clinical Cancer Research

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“…It was found that an elevated YB-1 amount correlates with expression of proliferation markers [33], YB-1 overexpression causes hyperplasia [34], and cell doubling time increases with decreasing YB-1 expression under the action of siRNAs [35]. But the opposite may be speculated too, i.e., that YB-1 synthesis decreases as a result of a slower cell division.…”

Section: Resultsmentioning

confidence: 99%

YB-1 Synthesis Is Regulated by mTOR Signaling Pathway

2012

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YB-1 is a eukaryotic protein with numerous intra- and extracellular functions based on its ability to interact with RNA, DNA, and many proteins. In spite of achievements in studying its functions, regulation of YB-1 synthesis in the cell remains poorly understood. In the current study Western and Northern blotting were used to determine the amounts of YB-1 and YB-1 mRNA in rabbit organs and several cell lines. As found, in the majority of studied eukaryotic cells a considerable proportion of YB-1 mRNA was stored in free mRNPs, i.e., was poorly translated. Also, we demonstrated that YB-1 synthesis depended on conditions that determined the rate of cell division. Specific suppression of YB-1 synthesis resulted from inhibition of the mTOR signaling pathway with inhibitor PP242, but not rapamycin. Experiments on reporter constructs showed that dependence of YB-1 mRNA translation on activity of the mTOR signaling pathway was dictated by 5′ untranslated regions of this mRNA, irrelatively of the TOP-like sequences at the beginning of 5′ UTR.

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“…Growing evidence indicates that abnormal growth of glomerular mesangial cells is an early event in various glomerular diseases and is the main histopathological feature in chronic kidney diseases (CKD) [1, 2]. Various signaling molecules are involved in mesangial cell proliferation and ECM accumulation [3-5].…”

Section: Introductionmentioning

confidence: 99%

Rosiglitazone Inhibits Angiotensin II-Induced Proliferation of Glomerular Mesangial Cells via the Gαq/Plcβ4/TRPC Signaling Pathway

Wei

Mao²,

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mesangial cell proliferation and extracellular matrix accumulation (ECM) deposition play an important role in the pathogenesis of glomerulosclerosis. TRPC and PPAR-γ can regulate cell proliferation. Angiotensin II (AngII) can induce mesangial cell proliferation and affect TRPC expression. However, the mechanism has not been fully elucidated. This study was designed to investigate the role of TRPC and the effect of rosiglitazone (RSG) in the proliferation of rat glomerular mesangial cells (HBZY-1) that were stimulated by AngII and the underlying mechanisms. Methods: Immunofluorescence staining and qRT-PCR were performed to examine the expression levels of TRPCs in HBZY-1. Gene expression levels of TRPC, PPAR-γ, RGS4 (regulators of G protein signaling), the GPCR/Gαq/PLCβ4/TRPC signaling pathway and major downstream molecules (PCNA, SKP2, P21 and P27) were detected by qRT-PCR and western blotting. Additionally, changes in intracellular Ca²⁺ levels were determined through Fluo-4 Ca²⁺ imaging, and the cell cycle was analyzed by flow cytometry. Results: Our results found that TRPC1 and 6 were at higher expression levels in HBZY-1 cells. Following AngII stimulation, there were increased levels of TRPC1 and 6, Ca²⁺ entry, PCNA and SKP2, decreased expression levels of P21 and P27 and a reduced G₀/G₁ percentage. Silencing TRPC1 and 6 by siRNAs led to decrease in Ca²⁺ influx, G₀/G₁ cell cycle arrest and cell proliferation. Notably, PPAR-γ activation by RSG upregulated RGS4 expression, which can interact with the Gαq family to inhibit the Gαq-mediated signaling cascade. The results were similar to silencing TRPC1 and 6 by siRNAs. Conclusion: All these results indicate that RSG could inhibit HBZY-1 cell proliferation via the Gαq/PLCβ4/TRPC signaling pathway.

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Y-Box Protein 1 Stimulates Mesangial Cell Proliferation via Activation of ERK1/2

Cited by 17 publications

References 69 publications

Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box–Binding Protein-1 Promotes Prostate Cancer Progression

Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box–Binding Protein-1 Promotes Prostate Cancer Progression

YB-1 Synthesis Is Regulated by mTOR Signaling Pathway

Rosiglitazone Inhibits Angiotensin II-Induced Proliferation of Glomerular Mesangial Cells via the Gαq/Plcβ4/TRPC Signaling Pathway

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