Knockdown endogenous CypA with siRNA in U2OS cells results in disruption of F-actin structure and alters tumor phenotype

Calhoun, Colonya Charolynn; Lu, Yingchun; Song, Jun; Chiu, Robert

doi:10.1007/s11010-008-9896-0

Cited by 22 publications

(22 citation statements)

References 34 publications

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“…In addition, it can also block any function of CyPA involving the area that CsA binds. As CsA is a widely used tool in research on CyPA and other cyclophilins, our results illustrate that it is a common misunderstanding that the inhibitory effect of CsA is simply viewed as the effect of blocking the PPIase activity of CyPA (39,40). In summary, our findings indicate that CyPA induces chemotaxis through a direct interaction with the ectodomain of CD147 in a PPIase-independent manner, suggesting that there exists a novel mechanism for CyPA to regulate cell signaling.…”

Section: Discussionmentioning

confidence: 54%

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Song

Zhang

Ren³

et al. 2011

Journal of Biological Chemistry

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Cyclophilin A (CyPA) is a ubiquitously distributed peptidylprolyl cis-trans isomerase (PPIase) that possesses diverse biological functions. Extracellular CyPA is a potent chemokine, which can directly induce leukocyte chemotaxis and contribute to the pathogenesis of inflammation-mediated diseases. Although it has been identified that the chemotaxis activity of CyPA is mediated through its cell surface signaling receptor CD147, the role of CyPA PPIase activity in this process is disputable, and the underlying molecular mechanism is still poorly understood. In this study, we present the first evidence that CyPA induces leukocyte chemotaxis through a direct binding with the ectodomain of CD147 (CD147 ECT ), independent of its PPIase activity. Although NMR study indicates that the CD147 ECT

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Section: Discussionmentioning

confidence: 54%

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Song

Zhang

Ren³

et al. 2011

Journal of Biological Chemistry

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“…Recently Lv et al demonstrated that actin dynamism is required for AngII-induced ROS generation in VSMC 26 . Additionally, knockdown of CyPA in U2OS cells showed actin structure disorganization resulting in decreased cell migration and proliferation 22 . Previous findings from our laboratory showed that a depletion of CyPA from VSMC inhibited cell migration and proliferation 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, CyPA has been shown to be a cell cytoskeleton binding protein 19, 20 by which it can regulate neutrophil migration 21 and tumorogenesis 22 through regulating actin polymerization. The role of intracellular CyPA in AngII-induced ROS production in VSMC is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Cyclophilin A Is Required for Angiotensin II–Induced p47phox Translocation to Caveolae in Vascular Smooth Muscle Cells

Soe

Sowden

Baskaran

et al. 2013

ATVB

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Objective Angiotensin II (AngII) signal transduction in vascular smooth muscle cells (VSMC) is mediated by reactive oxygen species (ROS). Cyclophilin A (CyPA) is a ubiquitously expressed cytosolic protein that possesses peptidyl prolyl cis-trans isomerase (PPIase) activity, scaffold function and, significantly enhances AngII-induced ROS production in VSMC. We hypothesized that CyPA regulates AngII-induced ROS generation by promoting translocation of NADPH oxidase cytosolic subunit p47phox to caveolae of the plasma membrane. Approach and Results Overexpression of CyPA in CyPA deficient VSMC (CyPA−/−VSMC) significantly increased AngII-stimulated ROS production. NADPH oxidase inhibitors (VAS2870 or diphenylene iodonium) significantly attenuated AngII-induced ROS production in CyPA and p47phox overexpressing CyPA−/−VSMC. Cell fractionation and sucrose gradient analyses showed that AngII-induced p47phox plasma membrane translocation, specifically to the caveolae, was reduced in CyPA−/−VSMC compared to WT-VSMC. Immunofluorescence studies demonstrated that AngII increased p47phox and CyPA colocalization and translocation to the plasma membrane. In addition, immunoprecipitation of CyPA followed by immunoblotting for p47phox and actin showed that AngII increased CyPA and p47phox interaction. AngII-induced p47phox and actin cell cytoskeleton association was attenuated in CyPA−/−VSMC. Mechanistically, inhibition of p47phox phosphorylation and PX domain deletion attenuated CyPA and p47phox interaction. Finally, cyclosporine A and CyPA-PPIase mutant, R55A, inhibited AngII-stimulated CyPA and p47phox association in VSMC suggesting that PPIase activity was required for their interaction. Conclusions These findings provide the mechanism by which CyPA is an important regulator for AngII-induced ROS generation in VSMC through interaction with p47phox and cell cytoskeleton which enhances the translocation of the p47phox to the caveolae.

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“…However, only the ERK inhibitor PD98059 was able to decrease the activation of NF-kB and attenuate the MMP-9 activity induced by CyPA (Jin et al 2004). Moreover, previous cancer cell line studies have demonstrated that CyPA secretion is associated with cancer cell proliferation, cell cycles progression, cell invasion, and the migration and inhibition of apoptosis (Choi et al 2007;Li et al 2008;Calhoun et al 2009). Interestingly, an overexpression of CyPA is associated with resistance to chemotherapeutic drugs.…”

Section: Discussionmentioning

confidence: 96%

The Expression of Cyclophilin A in Ovarian Endometrioma: Its Correlation with Recurrence and Vascularity

Usta

Turan

Adalı

2017

Tohoku J. Exp. Med.

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Endometriosis is defined as the presence of functional endometrial tissues outside of the uterine cavity. Ovarian endometrioma is the most common type of endometriosis. It is an estrogen-dependent inflammatory disease that frequently causes infertility and chronic pelvic pain. Cyclophilin A (CyPA) is secreted from various types of cells in response to inflammatory stimuli. Many previous studies have shown that the increased expression and/or heightened plasma levels of CyPA exacerbates inflammation. The aim of this study is to evaluate CyPA immunoreactivity in ovarian endometrioma cyst wall. In this cross-sectional study, CyPA immunoreactivity in endometrial tissue samples obtained from uterine cavity and in endometrioma cyst walls of 44 consecutive women with ovarian endometrioma were compared with control endometrial tissue samples obtained from uterine cavity of 40 women without endometrioma. All endometrioma samples were confirmed via histopathological examination. Finally, the relationship between CyPA immunoreactivity and the clinicopathological findings related to endometrioma were evaluated. The CyPA expression rates in glandular cells, stromal cells, and the capillary endothelium were significantly higher in endometrioma cyst walls of women with ovarian endometrioma than in the control endometrial tissue of women without endometrioma (p = 0.0002, p = 0.0417 and p = 0.0067, respectively). The correlation analysis demonstrated that glandular CyPA expression was correlated with endometrioma recurrence (p = 0.0267). However, stromal and vascular endothelial CyPA expression were correlated with dysmenorrhea recurrence (p = 0.0023 and p = 0.0003, respectively). In conclusion, the increased expression of CyPA in ectopic endometrial tissue is associated with endometrioma recurrences and vascularity.

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Knockdown endogenous CypA with siRNA in U2OS cells results in disruption of F-actin structure and alters tumor phenotype

Cited by 22 publications

References 34 publications

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity

Cyclophilin A Is Required for Angiotensin II–Induced p47phox Translocation to Caveolae in Vascular Smooth Muscle Cells

The Expression of Cyclophilin A in Ovarian Endometrioma: Its Correlation with Recurrence and Vascularity

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