Calcium Efflux Activity of Plasma Membrane Ca2+ ATPase-4 (PMCA4) Mediates Cell Cycle Progression in Vascular Smooth Muscle Cells

Afroze, Talat; Yang, Ge; Khoshbin, Amir; Tanwir, Mansoor; Tabish, Taha; Momen, Abdul; Husain, Mansoor

doi:10.1074/jbc.m113.533638

Cited by 26 publications

(16 citation statements)

References 50 publications

(36 reference statements)

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“…PMCA4 associated Ca 2+ efflux has been reported to be important for cell migration [16] as well as cell growth [41]-both important cancer hallmarks [17]. A gap closure assay was used to assess cell migration.…”

Section: Pmca4 Knockdown Inhibits Cell Migration Independent Of Cell mentioning

confidence: 99%

Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer

Sritangos

Alarcon

James

et al. 2020

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to standard treatments leading to poor patient survival. The expression of plasma membrane calcium ATPase-4 (PMCA4) is reported to modulate key cancer hallmarks including cell migration, growth, and apoptotic resistance. Data-mining revealed that PMCA4 was over-expressed in pancreatic ductal adenocarcinoma (PDAC) tumors which correlated with poor patient survival. Western blot and RT-qPCR revealed that MIA PaCa-2 cells almost exclusively express PMCA4 making these a suitable cellular model of PDAC with poor patient survival. Knockdown of PMCA4 in MIA PaCa-2 cells (using siRNA) reduced cytosolic Ca2+ ([Ca2+]i) clearance, cell migration, and sensitized cells to apoptosis, without affecting cell growth. Knocking down PMCA4 had minimal effects on numerous metabolic parameters (as assessed using the Seahorse XF analyzer). In summary, this study provides the first evidence that PMCA4 is over-expressed in PDAC and plays a role in cell migration and apoptotic resistance in MIA PaCa-2 cells. This suggests that PMCA4 may offer an attractive novel therapeutic target in PDAC.

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Section: Pmca4 Knockdown Inhibits Cell Migration Independent Of Cell mentioning

confidence: 99%

Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer

Sritangos

Alarcon

James

et al. 2020

Cancers

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“…Currently, a variety of factors have been shown to modulate the VSMC phenotype, such as microRNAs (miRNAs) (20), estrogen (21), oxidative stress (22) and Ca ²+ (23). Among these, the dual effects of estrogen on VSMC proliferation and migration have been reported (24).…”

Section: Introductionmentioning

confidence: 99%

IQGAP1 modulates the proliferation and migration of vascular smooth muscle cells in response to estrogen

Huang

Jin

Zhou

et al. 2015

International Journal of Molecular Medicine

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Abstract. Vascular smooth muscle cell (VSMC) proliferation and migration has been proven to be a critical event in the development of varicosity. Variations in estrogen levels, a pathological event related to age and pregnancy, play a role in the pathogenesis of varicosity. Previous studies have reported a different response of VSMCs following estrogen stimulation. However, the exact mechanisms involved have not yet been elucidated. In the present study, we examined the responses of lesion and normal VSMCs treated with 10 -8 M 17β-estradiol (E 2 ) for 24 h. A differential effect of exposure to E 2 was observed in these cells. IQ-domain GTPase-activating protein 1 (IQGAP1), a scaffold protein, was overexpressed in the lesion VSMCs and was shown to modulate VSMC proliferation and migration in response to E 2 . Furthermore, the increased expression of IQGAP1 was found to be intimately associated with a high activity of estrogen receptor α (ERα), which has been implicated in the regulation of VSMC physiological function. Additionally, we found that two critical kinases, Akt and extracellular signal-regulated kinase (ERK), mediated the activation of ERα and VSMC proliferation. According to our results, we thus concluded that high levels of IQGAP1 in VSMCs regulate the physiological reaction of the cells in response to estrogen exposure, and that kinases are involved in the process by mediating ERα activation. In view of the essential role of IQGAP1 in the physiological function of VSMCs, targeting this molecule may prove to be a promising strategy for the treatment of varicosity.

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“…Previous studies have confirmed that p15 and p16 are important factors regulating VSMC proliferation . Suv39h1 down‐regulation would promote p15 and p16 expression by inhibiting H3K9me3 in the promoter region, leading to inhibition of VSMC proliferation under pathological stimulation.…”

Section: Discussionmentioning

confidence: 89%

“…Previous studies have confirmed that p15 and p16 are important factors regulating VSMC proliferation. 39,40 Suv39h1 down-regulation would promote p15 and p16 expression by inhibiting H3K9me3 in the promoter region, leading to inhibition of VSMC proliferation under pathological stimulation. Unfortunately, there was no significant difference in H3K9me3 levels in the promoter of complement C3, which indicated that direct histone methylation was not the main mechanism of Suv39h1's effect on complement C3.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats

Zhang

Yang

et al. 2019

J Cellular Molecular Medi

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Patients with diabetes have an increased risk of vascular complications. Suv39h1, a histone methyltransferase, plays a protective role against myocardial injury in diabetes. Herein, we intend to explore whether Suv39h1 could affect neointimal formation after vascular injury in diabetic rats and reveal the underlying mechanism. In this study, we generated adenovirus expressing Suv39h1 as well as lentivirus expressing Suv39h1‐targeting shRNA and evaluated the significance of Suv39h1 in vascular smooth muscle cells (VSMCs) under diabetic conditions. In vitro, we examined proliferative and migratory behaviours as well as the underlying signalling mechanisms in VSMCs in response to high glucose treatment. In vivo, we induced diabetes in SD rats with streptozocin and established the common carotid artery balloon injury model. Suv39h1 was found to be both necessary and sufficient to promote VSMC proliferation and migration under high glucose conditions. We observed corresponding changes in intracellular signalling molecules including complement C3 and phosphor‐ERK1/2. However, either up‐regulating or down‐regulating Suv39h1, phosphor‐p38 level was not significantly affected. Consistently, Suv39h1 overexpression led to accelerated neointima formation, while knocking down Suv39h1 reduced it following carotid artery injury in diabetic rats. Using microarray analyses, we showed that altering the Suv39h1 level in vivo dramatically altered the expression of myriad genes mediating different biological processes and molecular function. This study reveals the novel role of Suv39h1 in VSMCs of diabetes and suggests its potential role as a therapeutic target in diabetic vascular injury.

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Calcium Efflux Activity of Plasma Membrane Ca2+ ATPase-4 (PMCA4) Mediates Cell Cycle Progression in Vascular Smooth Muscle Cells

Cited by 26 publications

References 50 publications

Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer

Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer

IQGAP1 modulates the proliferation and migration of vascular smooth muscle cells in response to estrogen

Down‐regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats

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