Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with β-catenin

Švastová, Eliška; Žilka, Norbert; Zaťovičová, Miriam; Gibadulinová, Adriana; Cĭampor, F; Pastorek, Jaromı́r; Pastoreková, Silvia

doi:10.1016/s0014-4827(03)00351-3

Cited by 220 publications

(219 citation statements)

References 44 publications

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“…When CA-IX expression was suppressed by siRNA in HCC cells, E-cadherin expression increased ( Figure 3C). This finding is compatible with that of a previous study, in which CA-IX was found to decrease E-cadherin levels in the Madin-Darby Canine kidney cell line [19] , and our results show that tumoral CA-IX intensity is inversely related to E-cadherin intensity. Altogether, these findings suggest that the induction of CA-IX expression may attenuate E-cadherin expression, thus leading to epithelial-mesenchymal transition potentiating invasiveness …”

Section: Decreased E-cadherin Expression By Ca-ix In Hcc Cellssupporting

confidence: 93%

“…Furthermore, when CA-IX expression was suppressed by siRNA, E-cadherin expression was increased. The ability of CA-IX to adhere to β-catenin [19] is consistent with the suggestion that hypoxia can promote tumor invasion by decreasing E-cadherin-mediated intercellular adhesion, offering the possibility that CA-IX participates in epithelial-mesenchymal transition [30,31] . Moreover, an alkaline intracellular pH and an acidic extracellular pH have been hypothesized to increase tumor growth [32] .…”

Section: Wwwchinapharcom Yu Sj Et Alsupporting

confidence: 85%

“…Acidic extracellular pH inhibits the binding of cells to CA-IX, suggesting that the CA-IX adhesion ability can be modulated by the tumor milieu [28] . CA-IX has also been implicated in intercellular adhesion [19] . In this previous study, it was found that CA-IX is localized with the key adhesion molecule E-cadherin, internalizes in response to the same external stimuli as E-cadherin, and reduces cell-to-cell adhesion by destabilizing the association between E-cadherin and the cytoskeleton through a method that involves direct binding of CA-IX to β-catenin [19] .…”

Section: Wwwchinapharcom Yu Sj Et Almentioning

confidence: 99%

“…CA-IX has also been implicated in intercellular adhesion [19] . In this previous study, it was found that CA-IX is localized with the key adhesion molecule E-cadherin, internalizes in response to the same external stimuli as E-cadherin, and reduces cell-to-cell adhesion by destabilizing the association between E-cadherin and the cytoskeleton through a method that involves direct binding of CA-IX to β-catenin [19] . In the present study, tumoral CA-IX intensity was found to be inversely related to E-cadherin intensity, increases of E-cadherin intensity may predict a favorable prognosis [29] .…”

Section: Wwwchinapharcom Yu Sj Et Almentioning

confidence: 99%

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Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase II inhibitor-induced hepatocellular carcinoma cell apoptosis

Yoon

Lee

et al. 2011

Acta Pharmacol Sin

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Aim:The hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, which could activate many signaling pathways and augment cancer cell growth and invasion. Carbonic anhydrase-IX (CA-IX) is an enzyme lowering pH. This study is to examine whether hypoxia induces CA-IX in hepatocellular carcinoma (HCC) cells, and to evaluate its clinical implication in HCC patients. Methods: Human HCC cell lines (Huh-7 and HepG2 cells) were used, and cell growth was assessed using MTS assay. CA-IX expression and apoptotic/kinase signaling were evaluated using immunoblotting. The cells were transfected with CA-IX-specific siRNA, or treated with its inhibitor 4-(2-aminoethyl) benzenesulfonamide (CAI#1), and/or the hexokinase II inhibitor, 3-bromopyruvate (3-BP). A clinic pathological analysis of 69 patients who underwent an HCC resection was performed using a tissue array. Results: Incubation of HCC cells under hypoxia (1% O 2 , 5% CO 2 , 94% N 2 ) for 36 h significantly increased CA-IX expression level. CAI#1 (400 µmol/L) or CA-IX siRNA (100 µmol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 µmol/L). This enhancement was attributed to increased ER stress and JNK activation, as compared with 3-BP alone. Furthermore, a clinic pathological analysis of 69 HCC patients revealed that tumor CA-IX intensity was inversely related to E-cadherin intensity. Conclusion: Inhibition of hypoxia-induced CA-IX enhances hexokinase II inhibitor-induced HCC apoptosis. Furthermore, CA-IX expression profiles may have prognostic implications in HCC patients. Thus, the inhibition of CA-IX, in combination with a hexokinase II inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment.

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Section: Decreased E-cadherin Expression By Ca-ix In Hcc Cellssupporting

confidence: 93%

Section: Wwwchinapharcom Yu Sj Et Alsupporting

confidence: 85%

Section: Wwwchinapharcom Yu Sj Et Almentioning

confidence: 99%

Section: Wwwchinapharcom Yu Sj Et Almentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase II inhibitor-induced hepatocellular carcinoma cell apoptosis

Yoon

Lee

et al. 2011

Acta Pharmacol Sin

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“…It catalyzes the reversible conversion of CO 2 to bicarbonate ion and proton like other active carbonic anhydrases, and participates in ion transport and pH control [Svastova et al, 2004]. Additionally, CA IX also reduces E-cadherin-mediated adhesion by binding to β-catenin [Svastova et al, 2003]. CA IX is a transmembrane isoform associated mainly with tumours, in contrast to other CAs that are present mostly in differentiated cells of normal tissues [Pastorek et al, 1994].…”

mentioning

confidence: 99%

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

Holotnakova¹,

Tylková²,

Takáčová³

et al. 2009

Journal of Medical Virology

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International audienceCarbonic anhydrase 9 (CA9), as one of the most hypoxia-responsive genes, has been associated almost exclusively with hypoxic tumours. Its principal role is in pH regulation which helps tumour cells overcome intracellular acidosis and survive extended periods of time with low oxygen. Hypoxia-inducible factor 1 (HIF-1) is the main transcriptional activator of CA9. Hepatitis B virus X protein (HBx) has been shown to increase the transcriptional activity of HIF-1. HBx is often expressed from the gene integrated in the hepatocytes infected persistently and contributes significantly to alterations in host gene expression that can lead to the development of hepatocellular carcinoma (HCC) associated with HBV. The aim of this study was to determine the effect of HBx on expression of CA9. Transient transfection of HBx led to an increase in the expression of CA9 as assessed by RT-PCR and Western blotting. HBx was able to increase CA9 promoter activity significantly in several cell lines. The effect was mediated via HIF-1 and a functional HRE element located –10/–3 bp upstream of the CA9 transcription initiation site. These data suggest that CA9 may be involved in the development of HCC by contributing to the survival of hepatocytes infected with HBV in liver tissue with fibrosis

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Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII

Pastoreková

Baráthová

Kopáček

et al. 2009

Drug Design of Zinc‐Enzyme Inhibitors

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Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with β-catenin

Cited by 220 publications

References 44 publications

Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase II inhibitor-induced hepatocellular carcinoma cell apoptosis

Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase II inhibitor-induced hepatocellular carcinoma cell apoptosis

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII

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