To investigate the role of zinc-finger protein 143 in cancer cells, we stably introduced ZNF143 expression knockdown by infecting colon cancer cells with short hairpin (sh) RNA-lentiviral particles against ZNF143 (HCT116 sh-ZNF143). Compared to sh-control cells, HCT116 sh-ZNF143 cells showed faster wound healing, increased migration through Transwell chambers, and increased invasion through Matrigel in Transwell chambers. ZNF143 knockdown increased transcriptional expression of ZEB1. Additionally, ZNF143 regulated E-cadherin transcriptional expression. Small interfering-RNA-mediated silencing of ZEB1 expression affected motility in HCT116 sh-ZNF143 cells. These data suggest that ZNF143 is involved in cellular motility through a ZEB1-E-cadherin-linked pathway in colon cancer cells.

We previously reported the involvement of zinc-finger protein 143 (ZNF143) on cancer cell motility in colon cancer cells. Here, ZNF143 was further characterized in breast cancer. Immunohistochemistry was used to determine the expression of ZNF143 in normal tissues and in tissues from metastatic breast cancer at various stages. Notably, ZNF143 was selectively expressed in duct and gland epithelium of normal breast tissues, which decreased when the tissue became malignant. To determine the molecular mechanism how ZNF143 affects breast cancer progression, it was knocked down by infecting benign breast cancer cells with short-hairpin (sh) RNA-lentiviral particles against ZNF143 (MCF7 sh-ZNF143). MCF7 sh-ZNF143 cells showed different cell-cell contacts and actin filament (F-actin) structures when compared with MCF7 sh-Control cells. In migration and invasion assays, ZNF143 knockdown induced increased cellular motility in breast carcinoma cells. This was reduced by the recovery of ZNF143 expression. Taken together, these results suggest that ZNF143 expression contributes to breast cancer progression.

Expression of zinc-finger protein 143 (ZNF143), a human homolog of the Xenopus transcriptional activator protein Staf, is induced by various DNA-damaging agents including etoposide, doxorubicin, and γ-irradiation. ZNF143 binds to cisplatin-modified DNA, and its levels are increased in cancer cells that are resistant to anticancer drugs, including cisplatin, suggesting that it plays a role in carcinogenesis and cancer cell survival. However, the mechanism of ZNF143 induction in cancer cells remains unclear. Both insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) have been reported to be overexpressed in cancer cells and to be related to anticancer drug resistance, but the identity of the relevant signaling mediators is still being investigated. In the present study, we observed that IGF-1 was able to induce ZNF143 expression in HCT116 human colon cancer cells and that wortmannin, an inhibitor of phosphatidylinositide 3-kinase (PI3-kinase), inhibited this induction, as did diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, and monodansylcardavarine (MDC), a receptor internalization inhibitor. Treatment with MDC decreased the IGF-1-stimulated generation of reactive oxygen species. Taken together, these data suggest that IGF-1 induces ZNF143 expression in cancer cells via PI3-kinase and reactive oxygen species generation during receptor internalization.

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Tight junction protein 1 (TJP1), a component of tight junction, has been reported to play a role in protein networks as an adaptor protein, and TJP1 expression is altered during tumor development. Here, we found that TJP1 expression was increased at the RNA and protein levels in TGF-β-stimulated lung cancer cells, A549. SB431542, a type-I TGF-β receptor inhibitor, as well as SB203580, a p38 kinase inhibitor, significantly abrogated the effect of TGF-β on TJP1 expression. Diphenyleneiodonium, an NADPH oxidase inhibitor, also attenuated TJP1 expression in response to TGF-β in lung cancer cells. When TJP1 expression was reduced by shRNA lentiviral particles in A549 cells (A549-sh TJP1), wound healing was much lower than in cells infected with control viral particles. Taken together, these data suggest that TGF-β enhances TJP1 expression, which may play a role beyond structural support in tight junctions during cancer development. [BMB Reports 2015; 48(2): 115-120]