Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling

Wang, Zhixiang

doi:10.3390/cells10123327

Cited by 108 publications

(73 citation statements)

References 185 publications

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“…In the absence of 10% FBS, almost complete dephosphorylation of AKT and ERK1/2 was observed in both Ctrl-PASMCs and MCT-PAH-PASMCs, which is consistent with previous findings [ 48 , 49 ]. AKT and ERK1/2 are the major mediators downstream of growth factor receptor signaling [ 50 ]. Thus, in the starvation state, AKT and ERK1/2 tend to be inactive.…”

Section: Discussionmentioning

confidence: 99%

The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways

Lian

Wang

et al. 2022

BMC Pulm Med

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Background The zinc transporter ZIP12 is a membrane-spanning protein that transports zinc ions into the cytoplasm from the extracellular space. Recent studies demonstrated that upregulation of ZIP12 is involved in elevation of cytosolic free zinc and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia. However, the expression of ZIP12 and its role in pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats have not been evaluated previously. The aim of this study was to investigate the effect of ZIP12 on the proliferation and migration of PASMCs and its underlying mechanisms in MCT-induced PAH. Methods A PAH rat model was generated by intraperitoneal injection of 20 mg/kg MCT twice at one-week intervals. PASMCs were isolated from the pulmonary arteries of rats with MCT-induced PAH or control rats. The expression of ZIP12 and related molecules was detected in the lung tissues and cells. A ZIP12 knockdown lentivirus and an overexpressing lentivirus were constructed and transfected into PASMCs derived from PAH and control rats, respectively. EdU assays, wound healing assays and Western blotting were carried out to explore the function of ZIP12 in PASMCs. Results Increased ZIP12 expression was observed in PASMCs derived from MCT-induced PAH rats. The proliferation and migration of PASMCs from PAH rats were significantly increased compared with those from control rats. These results were corroborated by Western blot analysis of PCNA and cyclin D1. All these effects were significantly reversed by silencing ZIP12. Comparatively, ZIP12 overexpression resulted in the opposite effects as shown in PASMCs from control rats. Furthermore, selective inhibition of AKT phosphorylation by LY294002 abolished the effect of ZIP12 overexpression on enhancing cell proliferation and migration and partially suppressed the increase in ERK1/2 phosphorylation induced by ZIP12 overexpression. However, inhibition of ERK activity by U0126 resulted in partial reversal of this effect and did not influence an increase in AKT phosphorylation induced by ZIP12 overexpression. Conclusions ZIP12 is involved in MCT-induced pulmonary vascular remodeling and enhances the proliferation and migration of PASMCs. The mechanism of these effects was partially mediated by enhancing the AKT/ERK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways

Lian

Wang

et al. 2022

BMC Pulm Med

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“…As such, three checkpoints (G1, G2, and M phases) are put in place to circumvent any defects in the genetic makeup of daughter cells. At the G1 phases, where cyclins D ensures that cells progressing to the S phase have the essential requirement ( 33 ), GDNF has been found to play vital roles in stimulating and regulating the cell to enhance their transition to the S phase ( 34 , 35 ). Also, during G2, where cyclins and p53 crosscheck the perfection of DNA replication and the absence of any damage before the cell enters the M phase, the involvement of SOX family members ( SOX1 , SOX2 ), and signal transduction activator of transcription 3 (STAT3) , CREB/CBP has been shown ( 36 , 37 ).…”

Section: Introductionmentioning

confidence: 99%

Cancer Metabolism: The Role of Immune Cells Epigenetic Alteration in Tumorigenesis, Progression, and Metastasis of Glioma

Kanwore

Adzika

et al. 2022

Front. Immunol.

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Glioma is a type of brain and spinal cord tumor that begins in glial cells that support the nervous system neurons functions. Age, radiation exposure, and family background of glioma constitute are risk factors of glioma initiation. Gliomas are categorized on a scale of four grades according to their growth rate. Grades one and two grow slowly, while grades three and four grow faster. Glioblastoma is a grade four gliomas and the deadliest due to its aggressive nature (accelerated proliferation, invasion, and migration). As such, multiple therapeutic approaches are required to improve treatment outcomes. Recently, studies have implicated the significant roles of immune cells in tumorigenesis and the progression of glioma. The energy demands of gliomas alter their microenvironment quality, thereby inducing heterogeneity and plasticity change of stromal and immune cells via the PI3K/AKT/mTOR pathway, which ultimately results in epigenetic modifications that facilitates tumor growth. PI3K is utilized by many intracellular signaling pathways ensuring the proper functioning of the cell. The activation of PI3K/AKT/mTOR regulates the plasma membrane activities, contributing to the phosphorylation reaction necessary for transcription factors activities and oncogenes hyperactivation. The pleiotropic nature of PI3K/AKT/mTOR makes its activity unpredictable during altered cellular functions. Modification of cancer cell microenvironment affects many cell types, including immune cells that are the frontline cells involved in inflammatory cascades caused by cancer cells via high cytokines synthesis. Typically, the evasion of immunosurveillance by gliomas and their resistance to treatment has been attributed to epigenetic reprogramming of immune cells in the tumor microenvironment, which results from cancer metabolism. Hence, it is speculative that impeding cancer metabolism and/or circumventing the epigenetic alteration of immune cell functions in the tumor microenvironment might enhance treatment outcomes. Herein, from an oncological and immunological perspective, this review discusses the underlying pathomechanism of cell-cell interactions enhancing glioma initiation and metabolism activation and tumor microenvironment changes that affect epigenetic modifications in immune cells. Finally, prospects for therapeutic intervention were highlighted.

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“…Extrinsic and intrinsic factors regulate the cell cycle culminating in the activation of cyclindependent kinases, CDKs, by the binding to their regulatory cyclins that together drive the cell through the cell cycle [19][20][21][22]. The differential expression of cyclins throughout the cell cycle is mandatory for cell cycle progression [23,24].…”

Section: Introductionmentioning

confidence: 99%

“…The differential expression of cyclins throughout the cell cycle is mandatory for cell cycle progression [23,24]. Furthermore, cyclin-dependent kinase inhibitors, CKIs, antagonize cell cycle progression [22]. Extrinsic factors, as nutrients and growth factors, activate the mitogen-induced signaling pathway (MAPK pathway) and the serine/threonine-protein kinase B (PI3K/AKT) pathway eventually inducing transcription of cyclin D that binds and activates CDK4/6 thus initiating progression from G1 to S phase and cell proliferation [22].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, cyclin-dependent kinase inhibitors, CKIs, antagonize cell cycle progression [22]. Extrinsic factors, as nutrients and growth factors, activate the mitogen-induced signaling pathway (MAPK pathway) and the serine/threonine-protein kinase B (PI3K/AKT) pathway eventually inducing transcription of cyclin D that binds and activates CDK4/6 thus initiating progression from G1 to S phase and cell proliferation [22]. On the other hand, low nutrient levels favour cell cycle arrest by increased AMP/ATP and ADP/ATP ratios which activate the energy-sensing AMP-activated protein kinase, AMPK.…”

Section: Introductionmentioning

confidence: 99%

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FOXA1 is a transcriptional activator of Odf2/Cenexin and regulates primary ciliation

Hoyer‐Fender

Czerny

Borschel

et al. 2022

Preprint

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Primary cilia are sensory organelles essential for embryonic and postnatal development, and tissue homeostasis in adulthood. They are generated in a cell cycle-dependent manner and found on most cells of the body. Although cilia formation is intensively investigated virtually nothing is known about the transcriptional regulation of primary ciliation. We used here Odf2/Cenexin, encoding a protein of the mother centriole and the basal body that is mandatory for primary cilia formation, as the starting point for the identification of transcriptional activators. We identified a consensus binding site for Fox transcription factors (TFs) in its promoter region and focused here on the Fox family. We found transcriptional activation of Odf2 neither by FOXO TFs nor by the core TF for multiciliation, FOXJ1. However, we identified FOXA1 as a transcriptional activator of Odf2 by reporter gene assays and qRT-PCR, and showed by qWB that Foxa1 knockdown caused a decrease in ODF2 and CP110 proteins. We verified the binding sequence of FOXA1 in the Odf2 promoter by ChIP. Finally, we demonstrated that knockdown of FOXA1 affected primary cilia formation. We, thus, showed for the first time, that FOXA1 regulates primary ciliation by transcriptional activation of ciliary genes.

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Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling

Cited by 108 publications

References 185 publications

The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways

The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways

Cancer Metabolism: The Role of Immune Cells Epigenetic Alteration in Tumorigenesis, Progression, and Metastasis of Glioma

FOXA1 is a transcriptional activator of Odf2/Cenexin and regulates primary ciliation

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