Significant relevance of overexpression of Pyk2 and disease-free

Significant relevance of overexpression of Pyk2 and disease-free survival was first demonstrated in the current clinical expression study. Consistent with the poor prognosis, patients with higher levels of Pyk2 showed aggressive new product tumour progression, advanced tumour staging and more invasiveness. Positive correlation between Pyk2 and FAK was also found in our study. In addition to the detection of Pyk2 and FAK in the liver tumour and non-tumour tissues, the gene expression levels of ezrin and fibronectin, two potential metastatic genes, were also investigated according to patients’ different expression levels of Pyk2. Ezrin, as a key determinant of tumour metastasis, has been implicated as a conduit for signals between metastasis-associated cell surface molecules and signal transduction components (Hunter, 2004; Khanna et al, 2004).

Furthermore, recent study demonstrated the co-operative effect of ezrin and c-Src, which also correlated with Pyk2, in cancer cells, in cancer cell metastases (Elliott et al, 2004). In this study, higher expression levels of ezrin were found to be consistent with overexpression of Pyk2. Similarly, another gene, fibronectin, which plays important roles in the promotion of cancer cell survival, progression and metastasis, presented higher expression levels in patients with overexpression of Pyk2 (Thant et al, 2000; Fornaro et al, 2003; Han et al, 2006). The association of fibronectin and pyk2 has been reported previously (Loeser et al, 2003). The similar expression trend of the genes Pyk2 and FAK with ezrin and fibronectin might also suggest the potential role of Pyk2 in liver cancer metastasis/recurrence.

To confirm our findings in clinical samples, we further conducted in vitro functional studies and an in vivo animal study in an orthotopic liver tumour model with highly local (intrahepatic) and distant (lung) metastatic potential. Our animal study also first demonstrated that overexpression of Pyk2 was found in infiltrative liver tumour cells (local metastasis) and lung metastatic nodules. This in vivo animal study further confirmed the significant correlation of Pyk2 with HCC invasiveness. In addition to animal study, our primary function study also indicated that Pyk2 played important role in HCC cell proliferation and invasion.

However, Entinostat the distinct cell signalling pathways under the regulation of Pyk2 related to cell invasion and migration should be investigated to elucidate the exact molecular mechanism in addition to the phenomenon demonstrated in our clinical and animal studies. In summary, overexpression of Pyk2 and FAK was found in nearly 60% of HCC patients and was significantly correlated with poor prognosis. The significance of Pyk2 in HCC invasiveness was also demonstrated by our orthotopic liver cancer animal model with higher metastatic potential.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>