Focal Adhesion Kinase (FAK) Over-Expression and Prognostic Implication in Pediatric Hepatocellular Carcinoma

Int J Mol Sci. 2020 Aug 12;21(16):5795. doi: 10.3390/ijms21165795.


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.

Keywords: cirrhosis; enhancer of Zeste homolog 2; focal adhesion kinase; normal liver; pediatric hepatocellular carcinoma; β-Catenin.

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Nucleus / pathology
  • Child
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism
  • Humans
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Lysine / metabolism
  • Male
  • Methylation
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Prognosis
  • Proliferating Cell Nuclear Antigen / metabolism
  • Tumor Burden
  • Up-Regulation / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • CTNNB1 protein, human
  • Histones
  • Proliferating Cell Nuclear Antigen
  • beta Catenin
  • Phosphotyrosine
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Focal Adhesion Protein-Tyrosine Kinases
  • Lysine