title: The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular carcinoma progression and recurrence.
abstract: Understanding the precise molecular mechanisms 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. In the current study, 49 patients with hepatocellular carcinoma (HCC) were included prospectively. Liver tumour and adjacent non-tumour tissues were detected for the expression of Proline-rich tyrosine kinase 2 (Pyk2), focal adhesion kinase (FAK), ezrin and fibronectin at protein and/or gene levels. Correlation between the expressions of Pyk2/FAK with the clinical pathological data was analysed. Protein expression of Pyk2 was also examined in a nude mice orthotopic liver tumour model with higher metastatic potential. There were 59% (29 out of 49) and 57% (28 out of 49) of HCC patients with higher levels of Pyk2 and FAK protein/gene expression, respectively. We observed a positive correlation between the protein and gene expression levels of Pyk2 and FAK (P=0.000, r=0.875). Overexpression of Pyk2 and FAK was significantly correlated with shorter disease-free survival. Patients with higher levels of Pyk2/FAK had larger tumour size and advanced Edmonson grading. In the animal studies, Pyk2 overexpression was found in infiltrative tumour cells and lung metastatic nodules. In conclusion, 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 confirmed by animal studies.
authors.affiliation: Centre of Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: C K
authors.initials: CK
authors.lastname: Sun
authors.forename: K T
authors.initials: KT
authors.lastname: Ng
authors.forename: B S
authors.initials: BS
authors.lastname: Sun
authors.forename: J W Y
authors.initials: JW
authors.lastname: Ho
authors.forename: T K
authors.initials: TK
authors.lastname: Lee
authors.forename: I
authors.initials: I
authors.lastname: Ng
authors.forename: R T P
authors.initials: RT
authors.lastname: Poon
authors.forename: C M
authors.initials: CM
authors.lastname: Lo
authors.forename: C L
authors.initials: CL
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Man
authors.forename: S T
authors.initials: ST
authors.lastname: Fan
mesh_terms: D000328:Adult; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018450:Disease Progression; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009368:Neoplasm Transplantation; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D005353:Fibronectins; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D000099149:Ezrin; C496050:PTK2 protein, human