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

Abstract

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. H epatocellular carcinoma (HCC) is the fifth most common cancer worldwide 1 and the third most common cause of cancer-related mortality. One of the reasons for this high mortality is that the tumour usually presents at a stage when curative surgery is no longer feasible because of intrahepatic or extrahepatic metastases. Although the 5-year survival of HCC patients who have undergone hepatectomy has improved in recent years, postoperative intrahepatic recurrence can still be as high as 43% by 2 years after resection, 2 presumably because of preexisting micro-metastases. 3 These observations underscore the urgent need to understand the molecular characteristics and related biological mechanisms in tumor cell dissemination.Despite extensive studies, the underlying genomic alterations in HCC remain poorly understood, 4-6 and few tumor suppressors or proto-oncogenes have been related to metastasis and recurrences. Utilizing genetic information derived from a cohort of 100 HCC tumors analyzed by chromosome-based comparative genomic hybridization (CGH), our group has previously shown several regional chromosome gains, especially over-representations

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

“…As PFTK1 is a novel member of the Cdc2 family, few studies have been performed to characterize its physiological function or biological importance. We defined a role for PFTK1 as a regulatory factor in the control of HCC cell migration (Pang et al, 2007). Although it has been long recognized that Cdc2 proteins have vital roles in the control of cell cycle transitions in eukaryotic cells (Kirschner, 1992;Pines, 1992;Solomon, 1993) and would be suspected to have minimal influence on cell migrations, in line with our findings, an earlier study also showed that upregulation of Cdc2 could enhance cell migration through activating cyclin B2 and caldesmon in promoting actin contractility (Manes et al, 2003).…”

“…7q21-q22 of HCC. Our earlier investigations by ectopic expression and gene knockdown experiments confirmed an important role for PFTK1 in the cellular invasiveness and motility of HCC cells (Pang et al, 2007). Nevertheless, the biological basis that underlies the action of PFTK1 in conferring cell migratory properties in HCC remains unknown.…”

“…The use of Hep3B was based on the fact that this cell line exhibits overexpression of PFTK1 and is highly invasive (Pang et al, 2007). Approximately 2000 spots were resolved by 2D gel and more than 95% spots could be matched across the 2D gel images.…”

“…Compared with normal liver controls, both Hep3B and HKCI-4 exhibit upregulation of PFTK1, whereas L02 elicits negligible expression. L02 was transiently transfected with expression construct of green fluorescent protein-tagged PFTK1 as reported previously (Pang et al, 2007). The protein expression of green fluorescent protein-fused PFTK1 protein was confirmed by western blot.…”

“…The protein expression of green fluorescent protein-fused PFTK1 protein was confirmed by western blot. The expression of PFTK1 in Hep3B was stably suppressed by vector-based short hairpin RNA interference according to method described (Pang et al, 2007). In HKCI-4 cells, PFTK1 expression was transiently suppressed using siRNA obtained from Dharmacon (Chicago, IL, USA).…”