Role of CIP4 in high glucose induced epithelial--mesenchymal transition of rat peritoneal mesothelial cells

Zhang, Jian; Meisheng, BI; Zhong, Feng; Jiao, Xuelong; Zhang, Dianliang; Dong, Qi

doi:10.3109/0886022x.2013.808957

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…It has been shown that CIP4 promotes TGF-β1-induced EMT of renal proximal tubular epithelial cells [19] and mediates high glucose-induced EMT through PI3K-Akt signaling pathway in rat peritoneal mesothelial cells [20]. Moreover, knockdown of CIP4 strongly increases the formation of tubular E-cadherin vesicles at adherens junctions [21].…”

Section: Resultsmentioning

confidence: 99%

AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4

Liu

Xie

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Our previous studies have shown that PRKA kinase anchor protein 9 (AKAP-9) is involved in colorectal cancer (CRC) cell proliferation and migration in vitro. However, whether or not AKAP-9 is important for CRC development or metastasis in vivo remains unknown. In the present study, we found that AKAP-9 expression was significantly higher in human colorectal cancer tissues than the paired normal tissues. In fact, AKAP-9 level correlated with the CRC infiltrating depth and metastasis. Moreover, the higher AKAP-9 expression was associated with the lower survival rate in patients. In cultured CRC cells, knockdown of AKAP-9 inhibited cell proliferation, invasion, and migration. AKAP-9 deficiency also attenuated CRC tumor growth and metastasis in vivo. Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-β1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues. Taken together, our results demonstrated that AKAP-9 facilitates CRC development and metastasis via regulating CIP4-mediated epithelial-mesenchymal transition of CRC cells.

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Section: Resultsmentioning

confidence: 99%

AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4

Liu

Xie

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…CIP4 is overexpressed in normal epithelial cells undergoing the epithelial-mesenchymal transition (Zhang et al, 2013). CIP4 is also overexpressed in osteosarcoma (Koshkina et al, 2013), in chronic lymphocytic leukemia (Malet-Engra et al, 2013), in non-small cell lung cancer (Truesdell et al, 2014) and in a subset of invasive breast cancer cells (Pichot et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, CIP4 acts downstream of cdc42 activation to promote membrane deformation, vesicle scission and actin polymerization (Fricke et al, 2009), thus participating in endocytosis (Leibfried et al, 2008;Hartig et al, 2009;Feng et al, 2010), and in the formation of lamellapodial protrusions (Saengsawang et al, 2012) and pro-invasive invadopodia structures (Pichot et al, 2010;Hu et al, 2011). Regarding cell migration, CIP4 is upregulated during epithelial-mesenchymal transition (Zhang et al, 2013) and has been reported to be essential for the development of metastatic properties in different types of cancer cells (Pichot et al, 2010;Truesdell et al, 2014;Rolland et al, 2014;Koshkina et al, 2013). Although most studies point to its involvement in the formation of membrane structures that are necessary for cell migration, the actual mechanism by which CIP4 plays a central role in the acquisition of migratory properties has not been clarified yet.…”

Section: Introductionmentioning

confidence: 99%

Centrosomal AKAP350 and CIP4 act in concert to define centrosome/Golgi polarity in migratory cells

Tonucci

Hidalgo

Ferretti

et al. 2015

Journal of Cell Science

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The acquisition of a migratory phenotype is central in processes as diverse as embryo differentiation and tumor metastasis. An early event in this phenomenon is the generation of a nucleuscentrosome-Golgi back-to-front axis. AKAP350 (also known as AKAP9) is a Golgi and centrosome scaffold protein that is involved in microtubule nucleation. AKAP350 interacts with CIP4 (also known as TRIP10), a cdc42 effector that regulates actin dynamics. The present study aimed to characterize the participation of centrosomal AKAP350 in the acquisition of migratory polarity, and the involvement of CIP4 in the pathway. The decrease in total or in centrosomal AKAP350 led to decreased formation of the nucleus-centrosomeGolgi axis and defective cell migration. CIP4 localized at the centrosome, which was enhanced in migratory cells, but inhibited in cells with decreased centrosomal AKAP350. A decrease in the CIP4 expression or inhibition of the CIP4-AKAP350 interaction also led to defective cell polarization. Centrosome positioning, but not nuclear movement, was affected by loss of CIP4 or AKAP350 function. Our results support a model in which AKAP350 recruits CIP4 to the centrosome, providing a centrosomal scaffold to integrate microtubule and actin dynamics, thus enabling centrosome polarization and ensuring cell migration directionality.

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“…HG activates PI3K-Akt-mTOR pathway PI3K/Akt pathway is one of the most well known pathways upstream to mTOR and its activation has been implicated as an important mechanism in HGinduced EMT [36][37][38]. To further understand the underlying mechanism, we examined whether HG activated the PI3K-Akt-mTOR signaling pathway in RPMCs.…”

Section: Rapamycin Inhibits Rpmc Migration Enhanced By Hgmentioning

confidence: 99%

Rapamycin inhibits epithelial‐to‐mesenchymal transition of peritoneal mesothelium cells through regulation of Rho GTPases

Xiang

Xie

et al. 2016

The FEBS Journal

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Epithelial–mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a key process of peritoneal fibrosis. Rapamycin has been previously shown to inhibit EMT of PMCs and prevent peritoneal fibrosis. In this study, we investigated the undefined molecular mechanisms by which rapamycin inhibits EMT of PMCs. To define the protective effect of rapamycin, we initially used a rat PD model which was daily infused with 20 mL of 4.25% high glucose (HG) dialysis solution for 6 weeks to induce fibrosis. The HG rats showed decreased ultrafiltration volume and obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α‐smooth muscle actin (α‐SMA) and transforming growth factor‐β1. Rapamycin significantly ameliorated those pathological changes. Next, we treated rat PMCs with HG to induce EMT and/or rapamycin for indicated time. Rapamycin significantly inhibited HG‐induced EMT, which manifests as increased expression of α‐SMA, fibronectin, and collagen I, decreased expression of E‐cadherin, and increased mobility. HG increased the phosphorylation of PI3K, Akt, and mTOR. Importantly, rapamycin inhibits the RhoA, Rac1, and Cdc42 activated by HG. Moreover, rapamycin repaired the pattern of F‐actin distribution induced by HG, reducing the formation of stress fiber, focal adhesion, lamellipodia, and filopodia. Thus, rapamycin shows an obvious protective effect on HG‐induced EMT, by inhibiting the activation of Rho GTPases (RhoA, Rac1, and Cdc42).

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Role of CIP4 in high glucose induced epithelial--mesenchymal transition of rat peritoneal mesothelial cells

Abstract: This study shows that CIP4 promotes high glucose-induced EMT through PI3K-Akt signaling pathway in RPMCs.

Cited by 9 publications

References 28 publications

AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4

AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4

Centrosomal AKAP350 and CIP4 act in concert to define centrosome/Golgi polarity in migratory cells

Rapamycin inhibits epithelial‐to‐mesenchymal transition of peritoneal mesothelium cells through regulation of Rho GTPases

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