Novel identification of zyxin upregulations in the motile phenotype of hepatocellular carcinoma

Abstract

Genome-wide copy number aberrations are common in hepatocellular carcinoma, although the precise genetic events underlying disease progression remain poorly defined. Previous work from our group has indicated several regional chromosomal gains such as chromosome 7q34-q36 that are associated with advanced metastatic tumors. Although the distal chromosome 7q gains have also been implicated in the progression of other malignancies, information on underlying targeted genes is limited. In this study, we have examined the chromosome 7q34-q36 region for involved gene(s) (or genes of interest). An integrated array-based comparative genomic hybridization and transcriptional mapping analyses has enabled us to identify a single candidate, zyxin on chromosome 7q34-q36. This array-derived finding was supported by quantitative reverse transcription-polymerase chain reaction, which also indicated common upregulations of zyxin in hepatocellular carcinoma tumors compared to their corresponding nonmalignant liver tissue (17/52 cases; 33%). Although there was no correlation between zyxin expression and tumor stagings, there was a significant increase in messenger RNA levels in hepatocellular carcinoma cases that presented with multifocal disease (211.57936.9-fold) compared to those with solitary lesions (3.576.3-fold). Moreover, recurrence after resection was common in cases that displayed zyxin overexpressions in the initial resected tumor (P ¼ 0.05). Functional examination of zyxin by small interfering RNA-mediated knockdown in Hep3B cell line indicated a significant inhibition on cell migration through porous membrane (P ¼ 0.002) and invasion through matrigel-coated membrane (P ¼ 0.005). In summary, mapping of chromosome 7q34-q36 has led to the identification of frequent zyxin overexpressions in hepatocellular carcinoma, and a potential role for zyxin in conferring a motile phenotype.

Zyxin controls migration in epithelial–mesenchymal transition by mediating actin‐membrane linkages at cell–cell junctions

“…The differential effects of perturbed zyxin function on EMT in two model systems likely highlights distinct roles for zyxin at different cellular sites, namely focal adhesions/stress fibers and cell-cell adhesions. In fact, this may also explain why cancer progression has been associated with both increased and decreased zyxin expression in different model systems (van der Gaag et al, 2002;Amsellem et al, 2005;Sy et al, 2006).…”

Peptides in Low Molecular Weight Fraction of Serum Associated with Hepatocellular Carcinoma

“…Upregulation of zyxin in HCC tumors had been previously observed by quantitative reverse transcription-polymerase chain re- action [42]. Zyxin is a focal-adhesion-associated phosphoprotein with an apparent molecular weight of 82-84 kDa.…”

LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6

“…4 Previous studies showed that overexpression of PXN, TLN1, ZYX or PIK3R2 increases cell migration and/or metastasis in various cancer types including PCa. 5, 6, 7, 8 …”