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Identification of PFTAIRE protein kinase 1, a novel cell division cycle‐2 related gene, in the motile phenotype of hepatocellular carcinoma cells

Metastasis is a major cause of cancer morbidity and mortality in individuals with hepatocellular carcinoma (HCC), yet little is known about the underlying molecular basis. Using genetic information derived from chromosome‐based comparative genomic hybridization, we have reported previously on regional chromosome 7q21‐q22 gains in close association with HCC progression. In this study, we undertook cDNA microarray‐based comparative genomic hybridization, to examine the 7q21‐q22 region for the involved gene(s) in HCC. High‐resolution mapping analysis highlighted 7 candidates, namely PFTAIRE protein kinase 1 (PFTK1), ODAG, CDK6, CAS1, PEX1, SLC25A, and PEG10, within the region. Quantitative reverse transcription (RT)‐PCR evaluation further indicated upregulation of a single candidate gene, PFTK1, that correlated significantly with both advanced metastatic HCCs (P = 0.032) and tumor microvascular invasion (P = 0.012). Given that little is known about the function(s) of PFTK1, which is a novel cell division cycle (Cdc)2‐related gene, we examined its potential role in the motile phenotype of HCC cells by both ectopic expression and knockdown investigations. RNA‐interference knockdown of PFTK1 in invasive Hep3B cells resulted in a significant reduction in cell invasion, chemotactic migration, and cell motility (P < 0.001). Conversely, ectopic expression of PFTK1 in noninvasive HKCI‐C3 cells induced substantial cellular invasion and migration (P ≤ 0.007). In neither cell line was there any effect on cell viability. Immunofluorescence showed marked filamentous actin polymerizations in PFTK1‐expressing cells. Conclusion: In this study, we have thus provided preliminary evidence that overexpression of PFTK1 may confer a motile phenotype in malignant hepatocytes that accounts for the association of upregulation of this gene in metastatic HCC. (HEPATOLOGY 2007.)