TY - JOUR
T1 - Focal adhesion kinase (Fak) over-expression and prognostic implication in pediatric hepatocellular carcinoma
AU - Francalanci, Paola
AU - Giovannoni, Isabella
AU - Stefanis, Cristiano De
AU - Romito, Ilaria
AU - Grimaldi, Chiara
AU - Castellano, Aurora
AU - D’oria, Valentina
AU - Alaggio, Rita
AU - Alisi, Anna
N1 - Funding Information:
Funding: This research was funded by AIRC (Associazione Italiana per la Ricerca sul Cancro) to Anna Alisi with grant number MFAG12936. The study was also supported by Fondazione Bambino Gesù Onlus and European Union’s Horizon 2020 research and innovation program under grant agreement No 668596 (ChiLTERN).
Funding Information:
This research was funded by AIRC (Associazione Italiana per la Ricerca sul Cancro) to Anna Alisi with grant number MFAG12936. The study was also supported by Fondazione Bambino Ges? Onlus and European Union?s Horizon 2020 research and innovation program under grant agreement No 668596 (ChiLTERN).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/8/2
Y1 - 2020/8/2
N2 - 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.
AB - 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.
KW - Cirrhosis
KW - Enhancer of Zeste homolog 2
KW - Focal adhesion kinase
KW - Normal liver
KW - Pediatric hepatocellular carcinoma
KW - β-Catenin
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U2 - 10.3390/ijms21165795
DO - 10.3390/ijms21165795
M3 - Article
C2 - 32806748
AN - SCOPUS:85089647791
VL - 21
SP - 1
EP - 13
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 16
M1 - 5795
ER -