Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion

Çokaklı, Murat; Erdal, Esra; Nart, Denız; Yılmaz, Funda; Sağol, Özgül; Kilic, Murat; Karademir, Sedat; Atabey, Neşe

doi:10.1186/1471-2407-9-65

Cited by 106 publications

(111 citation statements)

References 33 publications

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“…However, studies in cancer patients and animal models have shown that in prostate, breast, lung, and pancreatic cancer, an increase in CAV1 expression is correlated with a poor prognosis and reduced survival (47)(48)(49)(50)(51). Several studies have shown a role for CAV1 in tumor invasion and metastasis (52,53). Recent studies in renal cell carcinoma cells showed that HIF-mediated induction of CAV1 expression is correlated with activation of EGFR signaling in a ligand-independent manner (24).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor/MAZ-Dependent Induction of Caveolin-1 Regulates Colon Permeability through Suppression of Occludin, Leading to Hypoxia-Induced Inflammation

Xie

Xue

Taylor

et al. 2014

Molecular and Cellular Biology

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c Caveolae are specialized microdomains on membranes that are critical for signal transduction, cholesterol transport, and endocytosis. Caveolin-1 (CAV1) is a multifunctional protein and a major component of caveolae. Cav1 is directly activated by hypoxia-inducible factor (HIF). HIFs are heterodimers of an oxygen-sensitive ␣ subunit, HIF1␣ or HIF2␣, and a constitutively expressed ␤ subunit, aryl hydrocarbon receptor nuclear translocator (ARNT). Whole-genome expression analysis demonstrated that Cav1 is highly induced in mouse models of constitutively activated HIF signaling in the intestine. Interestingly, Cav1 was increased only in the colon and not in the small intestine. Currently, the mechanism and role of HIF induction of CAV1 in the colon are unclear. In mouse models, mice that overexpressed HIF1␣ or HIF2␣ specifically in intestinal epithelial cells demonstrated an increase in Cav1 gene expression in the colon but not in the duodenum, jejunum, or ileum. HIF2␣ activated the Cav1 promoter in a HIF response element-independent manner. myc-associated zinc finger (MAZ) protein was essential for HIF2␣ activation of the Cav1 promoter. Hypoxic induction of CAV1 in the colon was essential for intestinal barrier integrity by regulating occludin expression. This may provide an additional mechanism by which chronic hypoxia can activate intestinal inflammation.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor/MAZ-Dependent Induction of Caveolin-1 Regulates Colon Permeability through Suppression of Occludin, Leading to Hypoxia-Induced Inflammation

Xie

Xue

Taylor

et al. 2014

Molecular and Cellular Biology

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“…Cav-1 is a palmitoylated lipid raft protein and has been found to interact with FASN in prostate cancer cells to promote tumor growth and survival (55). Recently, Cav-1 was also reported to promote the motility and invasion of hepatocellular carcinoma (HCC) and metastasis in a mouse model though an unknown mechanism (56,57). We therefore postulate that following HCV infection, FASN interacts with NS5B and, together with Cav-1, is recruited to lipid rafts, followed by the induction of signaling leading to hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Replication Is Modulated by the Interaction of Nonstructural Protein NS5B and Fatty Acid Synthase

Huang

Tseng

Liao

et al. 2013

J Virol

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Hepatitis C virus (HCV) is a positive-stranded RNA virus classified in the Hepacivirus genus in the family Flaviviridae. The 9.6-kb viral RNA genome encodes a precursor polyprotein that is processed to generate at least 10 viral proteins, including structural proteins (core, E1, E2, and p7) and nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) (1). The NS5B RNA polymerase, together with other nonstructural viral proteins (NS3, NS4A, NS4B, and NS5A) and host factors, constitutes the active replication complexes (RC) for viral RNA replication. These proteins are directly or indirectly associated with the endoplasmic reticulum (ER)-derived structure called the "membranous web," where replication occurs (2, 3). However, the exact host factors and detailed interactions within the RC remain to be determined.HCV infection usually causes chronic hepatitis and frequently leads to cirrhosis and hepatocellular carcinoma (HCC). Besides, HCV-induced end-stage liver disease is an important indication for liver transplantation in most of the Western countries (4, 5). At present, no effective vaccine to prevent HCV infection is available. The current treatment strategies for HCV infection are valid only for individuals with a particular single nucleotide polymorphism (SNP) in the interleukin-28B gene or for infections caused by certain viral genotypes (6). Accordingly, the prevalence of hepatic steatosis in HCV-infected patients is much higher than that in the general population or in hepatitis B virus (HBV)-infected patients (7). Hepatic steatosis has also been reported to be associated with an increased rate of HCC in chronic hepatitis C patients (8).Lipid metabolic pathways are essential for the entry, secretion, and replication of HCV. For example, apolipoprotein E (apoE) is essential for the production of HCVcc (HCV produced in cell culture) and for viral entry (9, 10). Downregulation of apoA-I decreases levels of HCV replication and viral particle production in cell culture (11). HCV coopts the secretory pathway of very low density lipoprotein (VLDL) for its own secretion (12, 13). Moreover, HCV replication is regulated through induction of lipogenic gene expression in HCV replicon cells (14) or geranylgeranylation of host proteins required for HCV RNA replication (15,16). Fatty acid synthesis is also required for HCV RNA replication (14). Inhibition of fatty acid synthase (FASN) by cerulenin (17) or C75 (18) reduces the replication of subgenomic HCV replicons as well as JFH-1-based HCVcc virion production. Although the underlying mechanisms are not yet completely understood, these studies imply that FASN is essential for HCV replication.In this study, HCV NS5B was used as the bait to screen for NS5B-interacting proteins that are present in Huh7 hepatoma cell lysates. After mass spectrophotometric analysis, FASN was found to interact with NS5B, and this interaction was further confirmed in vitro and in vivo. Our data indicate that FASN interacts with NS5B to enhance NS5B RNA-dependent RNA polymerase (RdRp) act...

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“…Cav-1 Expression-The absence of Cav-1 in well differentiated human HCC has been recently reported to be a specific signature of these cells (31). Accordingly, Cav-1 levels were analyzed in various hepatic cell lines, and although the hepatocytelike THLE-2 or CHL cells showed a significant expression of Cav-1 mRNA and protein, the HCC lines, such as HepG2 or HuH-7, failed to express this gene (Fig.…”

Section: Snon Protein Levels Are Increased In Hcc Human Cells That Lackmentioning

confidence: 99%

Impairment of Transforming Growth Factor β Signaling in Caveolin-1-deficient Hepatocytes

Mayoral

Valverde

Llorente

et al. 2010

Journal of Biological Chemistry

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signaling decreased in the absence of Cav-1 at the time that the transcriptional corepressor SnoN accumulates. Accordingly, the expression of TGF-␤ target genes, such as plasminogen activator inhibitor-1, is decreased due to the presence of the high levels of SnoN. Moreover, hepatocyte growth factor inhibited TGF-␤ signaling in the absence of Cav-1 by increasing SnoN expression. Taken together, these data might help to unravel why Cav-1-deficient mice exhibit an accelerated liver regeneration after partial hepatectomy and add new insights on the molecular mechanisms controlling the initial commitment to hepatocyte proliferation.

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Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion

Cited by 106 publications

References 33 publications

Hypoxia-Inducible Factor/MAZ-Dependent Induction of Caveolin-1 Regulates Colon Permeability through Suppression of Occludin, Leading to Hypoxia-Induced Inflammation

Hypoxia-Inducible Factor/MAZ-Dependent Induction of Caveolin-1 Regulates Colon Permeability through Suppression of Occludin, Leading to Hypoxia-Induced Inflammation

Hepatitis C Virus Replication Is Modulated by the Interaction of Nonstructural Protein NS5B and Fatty Acid Synthase

Impairment of Transforming Growth Factor β Signaling in Caveolin-1-deficient Hepatocytes

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