Focal adhesion kinase (Fak) over-expression and prognostic implication in pediatric hepatocellular carcinoma

Research output: Contribution to journalArticlepeer-review

Abstract

Focal adhesion kinase (FAK) is over-expressed and is correlated with aggressiveness in adult hepatocellular carcinoma (HCC). Inhibition of FAK decreases HCC invasiveness by down-regulating Enhancer of Zeste homolog 2 (EZH2), an epigenetic controller, that acts in transcriptional repression of a large number of genes via histone 3 methylation of lysine 27 (H3K27me3). Here, we investigated the hepatic expression of total FAK, EZH2, H3K27me3, and proliferating cell nuclear antigen (PCNA) in 17 pediatric HCCs and 8 healthy livers (CTRL). Quantitative imaging analysis showed that FAK gene/protein expression is up-regulated in HCCs compared to CTRL and, among tumor samples the levels of this gene/protein are significantly higher in cirrhotic HCCs than in a healthy milieu. Accordingly, the protein levels of EZH2 were also significantly increased in HCCs from a cirrhotic background. Intriguingly, the protein expression of FAK, EZH2, and PCNA significantly inversely correlated with tumor size. Finally, in HCC samples, mainly in cirrhotic background, the up-regulation of FAK gene positively correlated with that observed in β-Catenin gene. Conclusion: FAK gene/protein is over-expressed in pediatric HCCs concomitantly to EZH2 protein and β-Catenin gene, with a more significant up-regulation in a cirrhotic background. This triad of interactors deserves further investigations for translational application.

Original languageEnglish
Article number5795
Pages (from-to)1-13
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume21
Issue number16
DOIs
Publication statusPublished - Aug 2 2020

Keywords

  • Cirrhosis
  • Enhancer of Zeste homolog 2
  • Focal adhesion kinase
  • Normal liver
  • Pediatric hepatocellular carcinoma
  • β-Catenin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Focal adhesion kinase (Fak) over-expression and prognostic implication in pediatric hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this