The investigators collected all study data, had access to all data, and wrote the manuscript. Acknowledgments We acknowledge the Cancer Society of Finland and the Finnish Medical Association (Finska Volasertib cost L?kares?llskapet) for financial support.
Understanding the precise molecular networks that trigger liver cancer cell migration and invasion could develop novel therapeutic strategies targeting cancer cell invasion to increase the sensitivity to current treatment modalities. Focal adhesion kinase (FAK) is an important mediator of cell proliferation, cell survival and migration. Recently, clinical evidences demonstrated that FAK was involved in liver tumour progression and had prognostic significance for hepatocellular carcinoma (HCC) patients (Fujii et al, 2004; Itoh et al, 2004).

In addition to clinical relevance, animal experiments also demonstrated that FAK might play important roles in the regulation of metastatic adhesion of cancer cells with liver sinusoids and formation of organ-specific distant metastases. An in vitro study confirmed that FAK integrated growth-factor and integrin signals to promote cell migration (Sieg et al, 2000). An in vivo animal model also demonstrated that FAK is important for lung metastasis in a breast cancer model (van Nimwegen et al, 2005). Proline-rich tyrosine kinase 2 (Pyk2), also known as cell adhesion kinase�� (CAK��), is a tyrosine kinase that is structurally related to focal adhesion kinase (FAK) (Sasaki et al, 1995). Pyk2 has been demonstrated to be able to promote migration and invasion of glioma cells (Lipinski et al, 2005) as well as mediate angiogenesis of pulmonary vascular endothelial cells (Tang et al, 2002).

Moreover, Pyk2 also mediated vascular endothelial cadherin-based cell�Ccell adhesion and played an important role in the modulation of endothelial integrity (van Buul et al, 2005). However, neither expression study nor functional study of Pyk2 in HCC has been reported. It should be worthwhile to explore the potential role of Pyk2 in HCC metastases and recurrence. Recently, FAK became a potentially important new therapeutic target because of its overexpression in human tumours (McLean et al, 2005). To study the expression pattern of Pyk2 and its Brefeldin_A correlation with clinicopathological data will provide important information for development of novel therapies targeting at focal adhesion kinase family including Pyk2. In the current study, we investigated the correlation between the gene and protein expression levels of Pyk2 and FAK in liver tumour tissues with clinicopathological data, and examined the association of potential metastatic genes (ezrin and fibronectin) with Pyk2. We also explored the significance of Pyk2 in tumour invasiveness and metastases in animal models.